Can Guinea Pigs Have Strokes? The 41 Latest Answer

Like other small, furry pets, guinea pigs can hide symptoms of illness, and if you realize they’re sick, they can die. Recognizing the signs of a dying guinea pig is important for all guinea pig owners to protect their pets.

What are signs that a guinea pig is dying? Regardless of the disease or medical condition, the signs that a guinea pig is sick and dying are common with many types of health problems. If you see any of these signs in your guinea pig, don’t hesitate to take them to a veterinarian. A guinea pig suffering from a serious illness can die within 24 to 72 hours, so it’s important to pay attention to your guinea pig’s behavior and habits and exercise quickly to keep your guinea pig healthy. Related Articles 6 Common Cat Cold Symptoms and How to Treat Them

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Loss of appetite Guinea pigs that are very sick will refuse to eat and may show signs of weight loss if the loss of appetite persists for some time. You may also see your guinea pig avoid drinking water, which can quickly lead to serious dehydration. A good way to keep track of how much your guinea pig is eating is to invest in a small animal scale or baby scale and weigh them weekly. With a pet as small as a guinea pig, there doesn’t have to be a lot of weight loss to lead to serious health problems.

Bad Urine and Feces Some common signs of serious illness and possible death in guinea pigs are watery diarrhea and blood in the stool or urine. Straining to urinate or have a bowel movement are also signs that your guinea pig has a urinary or intestinal obstruction, or kidney disease and needs medical attention. Another common sign that is often overlooked is the production of fewer feces than normal and in smaller sizes. In other words, your pig may still defecate, but in smaller amounts, or the individual “chunks” of faeces will look smaller than normal. If you notice a noticeable difference in how much waste your guinea pig produces, talk to your veterinarian as soon as possible.

Fever A guinea pig with a fever is definitely seriously ill and will need treatment to keep it from dying. Fever is often a symptom of pneumonia, which has resulted in the death of a high percentage of guinea pigs.

Breathing Problems Any type of breathing problem can be a sign of a serious problem with your guinea pig. These include wheezing, wheezing, labored breathing, coughing, or sneezing. Difficulty breathing can also be a sign of pneumonia, which is one of the leading causes of death in guinea pigs.

Eye Disorders A sick guinea pig will develop a crusted substance around the eyes and sometimes around the nasal passages. Your eyes will also appear cloudy and dull, and may even appear sunken. You may also find that their eyes become inflamed and produce a discharge if your guinea pig has conjunctivitis, which is a common disease in the species.

Poor Coat Condition A sick and dying guinea pig will have a very poor coat that may appear dull, thinning, or rough. You may also have patches of hair loss and you may see areas of inflamed skin. You should also be on the lookout for signs of parasites such as ringworm, lice, and mites. Common areas for skin infestation are around the guinea pig’s head and anus.

Mobility Issues If your guinea pig is having trouble moving and showing signs of pain such as: B. limp or lack of coordination, it can be very ill. If you notice that your posture appears “hunched over,” this is another sign of pain and illness.

Lethargy If your guinea pig’s normal level of activity has dropped and it appears disinterested or unable to move around its cage, this indicates a life-threatening condition is present. You should also watch for slowness in responding to you or other stimuli added to the cage.

Changes in behavior Any noticeable change in your guinea pig’s behavior can be a sign that it is ill and in danger of death. Some common problem behaviors include depression, excessive hiding, staring into corners, or avoiding touch. Keep in mind that with a guinea pig, which is usually shy, this isn’t necessarily a problem as you’ll be looking for differences in your individual pet’s behavior from their normal routine.

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We have shown that the cerebral vasculature can be occluded by intra-arterial injection of thrombin proximal to the rete mirabile. It challenged a long-standing paradigm that stroke in pigs cannot be induced using an endovascular approach. Initially, there was great uncertainty as to whether perfusion blockage in rete, cerebral vessels would occur or not occur at all. To address this issue, we leveraged our previously established interventional MRI approaches, which have proven excellent for monitoring intra-arterial targeting20. With this approach, we were able to see in real time during the procedure if and when cerebral vessels were blocked. The addition of gadolinium-based contrast agent to thrombin facilitated dynamic imaging and visualization of thrombus formation, which was evidenced by the persistence of a hypointense signal after the infusion was complete. The position of the thrombus was then confirmed using a high-resolution SWI sequence. Thrombin/Gd solution infused at a constant rate was cleared from the vasculature and the pulsatile infusion induced coagulation more effectively. MR imaging after thrombin injection showed early changes in ADC, shortly after clot induction. Using this image-guided approach, we were able to induce ischemia with high reproducibility. Our model has unique features and an advantage over existing craniotomy-based models of ischemic stroke. Bone removal and rupture of the dura mater affect intracranial pressure, lead to loss of cerebrospinal fluid, and increase the risk of infection. Animals post-surgical stroke often require critical care for symptoms other than stroke-related neurological deficits21. Our method is relatively short, minimally invasive, precludes extensive non-stroke morbidity due to the surgical procedure, and as such improves clinical relevance. The time from skin incision to placement of the microcatheter in the ascending pharyngeal artery was less than one hour. The duration of the entire procedure was no more than 4 hours. The ischemic region was typically quite large and, as expected, this is associated with a relatively high mortality. This level of mortality may be associated with edema and herniation, as evidenced by longitudinal cerebral fissure displacement 24 h after stroke induction (shown in Fig. 2). Mortality in craniectomy-based models is lower because trepanation mitigates the effects of intracranial pressure spikes, but as such removes the clinical relevance of surgical models. In our study, two out of nine pigs developed severe morbidity after ischemia and died within 24 h. Another animal was in relatively good condition at 24 h but died during the subsequent MRI scan due to post-anaesthesia respiratory depression. This approximately 33% mortality is comparable to that observed in surgical models or with rodent MCAO models22,23,24. This relatively high mortality rate could potentially be reduced in the future by using a lower concentration or a reduced volume of intra-arterially injected thrombin.

Sheep and pigs mostly use craniotomy and craniectomy to induce stroke16,25,26. Few models of stroke exist using non-human primates, dogs, sheep, or even pigs. The use of non-human primates is considered controversial and impractical in many countries due to restricted laws. However, there are few models of ischemia in NHP27,28.

In addition to rodents, endovascular models of stroke have also been described in rabbits29, dogs30 and primates31, all of which are characterized by a favorable human-like cerebral vasculature. There have also been attempts to perform endovascular procedures in pigs19, but these have been complicated by vascular rete. Jahan et al.29 developed selective middle cerebral artery (MCA) occlusion in rabbits using a similar approach. They injected thrombin mixed with rabbit brain thromboplastin directly into the middle cerebral artery (MCA). MCA occlusion was achieved as confirmed by angiography. Jahan et al.29 did not assess whether the procedure results in ischemia, but they used this model to demonstrate pharmacological thrombolysis using intra-arterially administered plasmin. In dogs with much larger arteries, there is more flexibility in navigating the catheter, and two ways to occlude the canine MCA have been reported with access via the internal carotid artery32 or via the vertebral artery (VA)33. Stroke volume in dogs with ICA emboli injection varies with clot size and was greatest in the 1.4mm/1.7mm clot group combined with additional temporary ipsilateral ICA occlusion (4173.23 ± 603.22 mm3 )14.32. Despite the collateralization of blood vessels within the rete mirabile in pigs or sheep, there have been few attempts to direct embolic material beyond the rete mirabile. Ringer et al.19 showed that autologous thrombus was injected into the ascending pharyngeal artery. They angiographically confirmed closure of APA; However, they did not perform confirmation of ischemic injury, which is unlikely given the contralateral contribution. Gralla34 used pigs as a model for mechanical thrombectomy in acute stroke. In this case, they injected a clot into the maxillary artery (MA), resulting in a far distal obstruction, and tested the feasibility of clot removal with a clot removal device. Recent analysis by Herrmann et al.35 showed that only 2.7% of the analyzed large animal studies used a follow-up period of up to 1 week and 36.5% used a follow-up period of 3 to 6 months. Only 6.9% of studies were conducted in large animals using MRI to monitor model performance. Our entire study was guided with imaging to ensure precision, including navigating the catheter under the C-arm followed by MRI guidance to observe clot formation and stroke evolution over time. We observed the animals for up to 3 months. Important advantages of our endovascular stroke model compared to other reported large animal models include the minimally invasive approach, assessment of the very early stroke-related tissue changes with imaging, and the potential to utilize IA catheter placement for local delivery of adjuvant therapies, including stem cells36. The last feature is very attractive in the age of increasing use of thrombectomy37. We observed a fairly large range of stroke lesion sizes with a mean infarct volume of 7.39 ± 5.41. However, this variability is consistent with clinically observed stroke as well as other swine studies38 showing mean lesion volumes of 18.25 ± 12.02 cm3.

We have performed a long-term assessment of BBB status and our IF data clearly indicate chronic-stage BBB disruption. This sustained BBB opening is likely associated with and contributes to progressive neuroinflammation, degeneration, and astrocytic scarring. This could be an important therapeutic goal as some long-term patient follow-up studies report opening of the BBB up to 90 days after ischemic stroke39.

Rodents remain the most widely used approach to study stroke11 and to determine the effectiveness of various drug therapies. However, the inadequacy of these preclinical models has been considered to be the main reason for the unsuccessful translation of experimental stroke therapies into the clinic12. An example of this discrepancy is cell transplantation approaches. Preclinical rodent experiments often show significant functional recovery and reduction in MCAO lesion volume, such as B. after intravenous injection of MSCs40,41. However, clinical trials following these protocols show only marginal or no benefit42,43 The issue of animal model adequacy has been addressed by the Stroke Treatment Academic Industry Roundtable (STAIR) Committee by publishing its recommendations. According to these recommendations, preclinical studies should be conducted using animal models mimicking clinical ischemic stroke, and the efficacy and safety of the tested therapy should be verified in at least two types. Due to ease of use, rodents can be used for initial screening, with strong recommendation for validation in large animal models12.

There are some limitations of this study. First, we focused here on the feasibility of inducing cerebral ischemia without reperfusion. Further studies are needed on the extent of reperfusion and whether this model is suitable for inducing pharmacological thrombolysis by the intra-arterial or intravenous route. However, we anticipate that pharmacological thrombolysis will be effective in this model since freshly induced thrombi should be easier to lyse compared to better organized thrombotic material detached from distant sites. Studies of reperfusion in this model will be important, particularly given the growing role of mechanical endovascular thrombectomy and the prospect of using intra-arterial adjuvant treatments after reperfusion. On the other hand, a meta-analysis by Cui et al.44 showed the need for clinically relevant models of permanent occlusion. Second, this study was conducted on young animals because mature or aging pigs are difficult to handle in such a study. Using older mini pigs could be a good solution. Access to advanced imaging equipment and neuroradiological expertise can be a limitation; However, as interest in endovascular stroke treatment grows, access to infrastructure and expertise is improving. Third, this study was conducted on a relatively small group of animals. We were able to demonstrate with this number of animals how the rete mirabile challenge for stroke induction can be met, but obviously further testing is needed to assess the feasibility, reproducibility, and usefulness of the model for studies of reperfusion and novel therapeutic approaches to confirm.

In conclusion, this study has provided for the first time the feasibility of inducing an endovascular stroke model in pigs. We could observe in real time the formation of a thrombin-induced clot and the resulting blockage of cerebral perfusion and finally a stroke lesion. Our model generated a relatively large infarct volume covering most of the MCA territory. Overall, we have established a new model of ischemic stroke in pigs with high clinical relevance. The model will contribute to studies aimed at understanding the pathophysiology of stroke and, more importantly, the development of new drugs.

A sick guinea pig may not be drinking enough water to stay healthy. Your guinea pig may be dehydrated if you notice any of these problems: thick, sticky saliva, crusty eyes, loss of appetite, small amounts of dark-colored urine, or hard, dry fecal pellets.

To compensate for dehydration, your guinea pig will need to be given extra water. Sometimes this can be accomplished by using a syringe to help the guinea pig drink. Some guinea pigs need to be given fluids by other means, either through subcutaneous fluids, intravenous fluids, or intraosseous fluids.

Using a syringe to help your pig drink

A guinea pig can drink from a syringe stuck in the corner of its mouth. The water should be offered slowly with frequent pauses to allow the animal to swallow and rest. If your mouth just starts to water, stop what you are doing. Try again in 30 minutes. If the guinea pig is still not drinking or is drinking less than 1 ounce of water per pound of body weight 2 to 3 times a day, your vet may prescribe subcutaneous fluids.

How to give subcutaneous fluids

Subcutaneous fluids are fluids that are injected under the skin. They may be abbreviated as SQ fluids or SC fluids. This can be used for a guinea pig that is still awake and not in critical condition. SQ liquids may be something your veterinarian might want you to give your guinea pig at home.

Different types of fluids can be used in different situations. Lactated Ringer’s solution and saline are two of the most commonly used SQ fluids.

To administer SQ fluids, you should wrap your guinea pig in a towel. The towel should be slightly loose but prevent the guinea pig from walking backwards or suddenly moving forward. Make sure your guinea pig can breathe easily in the towel. To administer the fluids, expose the skin over the guinea pig’s shoulders. Pinch the skin with your index fingers so that a small “tent” of skin rises above the shoulders. The needle should be inserted from back to front in the inverted “V” below the skin tent. Advance the needle to about half its length and then try to administer the liquid. If you have been given a syringe, press the syringe plunger firmly. If you received a bag of fluid, open the valve on the fluid line and squeeze the bag. If the liquids flow easily, you are successful. If hydration is difficult or your guinea pig is unwell, you may not have the needle in the right place and should slowly advance or remove it and try again. When you have finished administering the liquid, withdraw the needle and gently push into the hole where the needle was to prevent liquid from dripping onto the skin.

A bag of liquids should be discarded within 30 days after first use. If at any point you notice the fluid bag is cloudy, throw it out and get a new one.

Intravenous and intraosseous fluids

Some guinea pigs have medical conditions that require a constant supply of fluids directly into their system. These guinea pigs are in critical condition and would not do well on SQ or oral fluids alone.

Intravenous fluids (IV fluids) are given through a catheter inserted into a vein in the guinea pig’s forearm or leg. Intraosseous fluids (IO fluids) are given through a catheter inserted into the bone marrow of an arm or leg. Fluids given this way must be closely monitored to ensure the guinea pig is not getting too much or too little. In most situations, the guinea pig will need to remain in the hospital while receiving IV or IO fluids so technicians and doctors can respond to sudden changes.

Grief

Losing a friend can be very hard on lone pigs, especially when it’s always been just the two of them. Losing a companion can be very upsetting and stressful for your guinea pig, just as losing a friend can be for you or me. The deceased guinea pig may be the only other guinea pig friend your surviving piggy can remember and the shock of losing them would never have been something they ever dreamed of.

Just like us, guinea pigs can act and behave differently after the death of a friend. If your deceased guinea pig had multiple friends and was in a flock, the other pigs’ reaction may not be as bad as they will be comforted by others, although they are very likely to still feel some kind of loss after their friend passed away.

That’s a question I get asked a lot and I often take calls about it. It’s not something you want to talk about or even think about until it happens to you or you’ve been through that process before. Unfortunately, it’s inevitable that your guinea pig will eventually cross the rainbow bridge. That’s why we put this page together to answer as many questions as possible about what to do when your guinea pig dies. If I forwarded this link to you, you are most likely going through this right now and I hope this can help you with some of your questions.

Let your guinea pig understand what happened

If you find that your guinea pig died during the night, your surviving guinea pig would have been with them and could understand what happened. Sometimes you will find your guinea pig snuggling up to you; try to keep them warm. If this is the situation you encountered this morning, it can be really annoying for you. The shock of something you didn’t expect can have you all day or even every six and seven days afterwards. We’ve all been there and we totally understand how upsetting it is. Crying for days like we’re kids again even though I’m in my 50’s. But we have to pull ourselves together and think about our other guinea pig.

On the other hand, if your guinea pig died at the vet and hasn’t come home, your surviving guinea pig is no the wiser of what happened and they can wait and wait for days for your guinea pig to come home.

When a guinea pig dies it is important that the remaining guinea pigs get a goodbye, if at all possible. Place the surrendered guinea pigs back in their cage or hutch for just a few minutes for this to happen. They can ignore their friend, or look from afar, or nudge them to try and wake them up. It’s all part of the understanding process.

Will my other guinea pig be okay?

There is no definite answer to that, as I said before, we all react differently.

Remember that guinea pigs are social animals and love to be around their own kind. 95% of guinea pigs do not do well on their own if they have previously bonded with another guinea pig and need at least one friend. Imagine how lonely you would be if you lived your entire life without anyone to talk to and interact with.

We recommend finding a partner for your single piggie. It can be tough and even stressful at times for a while, but your guinea pig will be so much happier about it.

What to do right away for your guinea pig when it loses a friend.

A guinea pig will grieve and mourn just like us humans. Here are some things you can do to help your guinea pig right away after losing a friend.

1-Clean their cage. If they can’t smell their mate, this helps.

2-Give them an old teddy bear for company and cuddles.

3-If you can. Move their cage or coop around so they have something new to look at and examine.

4- Provide more entertainment, more cuddles and attention, extra treats, new toys, etc

5- Leave the radio on for them when you go out if they are in your house.

Signs your guinea pig is grieving and needs help

You should keep a close eye on your guinea pigs to make sure they are okay. Some guinea pigs can become quite ill after the death of a lifelong friend and the given time can also pass within a few weeks or months. If your piggy is showing any of the following signs of grieving, you need to act immediately.

1-They may give up their food because they don’t want to eat for a while. If they’re eating but not their usual amount, that’s not too much of a problem, but if they stop eating altogether, take them to a veterinarian for a check-up as soon as possible

2-They can sit still and not be their normal happy selves and look sad.

3-There may be a change in their behavior and personality.

These are all signs that your guinea pig is not doing very well on his own and needs a companion as soon as possible.

Guinea pigs have many appealing qualities: they are small, gentle, and personable, to name a few. However, like all pets, they require special care and attention. Here are some important questions to consider before adopting a guinea pig:

Where should you get a guinea pig from?

Rather than creating more demand for guinea pigs by purchasing one from a pet store, please visit your local animal shelter to adopt one – or better yet, two! Most animal shelters will accept small animals in need of a new home and you will have the satisfaction of saving a life.

Guinea Pig Accessories on Amazon.com

How much time do you have?

Guinea pigs need a break from their cage every day. Whether that time is spent stretching their legs and exploring new surroundings or snuggling on your lap, daily interaction and attention are essential to a guinea pig’s well-being.

Guinea pigs need regular grooming. Short haired breeds can be groomed with a weekly brush while long haired breeds need daily grooming.

A guinea pig’s cage should be given a deep cleaning weekly and spot cleaning every few days. If you don’t like the smell of a dirty cage, consider how smelly living quarters make your guinea pig — who spends most of their waking hours just inches from their bed — feel.

Is a Guinea Pig Right for Your Family?

If you are getting a guinea pig for your child, consider how caring for this animal fits into your family’s long-term schedule.

Q:

My guinea pig won’t eat, doesn’t exercise much and rarely has a bowel movement. If he has a bowel movement, it’s diarrhea. He is extremely skinny and weak. He was fine until recently. I’m really worried and not sure what to do for him. I intend to take him to the vet as soon as possible, but is there anything I can do for him in the meantime?

A:

It sounds like your guinea pig is very, very sick. Regardless of the cause of anorexia, if a guinea pig does not eat, it will also develop a liver disease called hepatic lipidosis. So, on top of what’s causing the disease, you’re now dealing with liver disease in this little fella.

Not eating, not moving, and reduced fecal production are considered nonspecific signs of illness. This means that any illness can lead to the signs you see in your guinea pig. This can be dental disease, liver disease, kidney disease, cancer, toxins, infections – the list goes on.

At the vet’s office, your vet will perform a full physical exam and will likely suggest blood work and x-rays. He or she may even want to do a stool exam because you’re reporting diarrhea, which can quickly debilitate a guinea pig.

The most important thing is to provide your guinea pig with fluids and calories until you can visit your vet. Do whatever you can to encourage drinking. Make sure the water bottle or bowl is always full. Consider using a solution like Pedialyte, which is tasty and contains extra nutrients. You also need to provide your guinea pig with calories and fiber. Call your vet’s office and ask if they have any products in stock that you can use. Many nutritious and balanced diets are now available for small mammals that require calories and fiber. Your vet can carry them, or you can find some at pet food stores as well.

But the best advice is to take your guinea pig to the vet much sooner rather than later. Guinea pigs that lose weight, don’t eat, and don’t exercise are very, very sick. The longer you wait to take the picture, the worse his prognosis will be. Instead of trying home remedies, seek immediate veterinary care.

By: Karen Rosenthal, DVM, MS

Featured image: DevMarya/iStock/Thinkstock

Guinea pigs are typically very active pets who like to exercise a lot in and out of their cage.

But have you ever noticed one of your guinea pigs taking a break from running around to lie flat for a while? Why do guinea pigs lie flat?

Guinea pigs lie flat because they feel safe and comfortable enough with you and their surroundings and just want to lie still and relax for a while.

Most of the time, it’s not a problem when a guinea pig lies flat because it just shows that they’re peaceful enough to relax outdoors.

However, there are also situations where lying flat can mean that there is a problem with them and you may need to step in and do something to keep your guinea pig happy and healthy.

These times are rare, but I’ll cover them in this article anyway so you can spot the signs.

Why do guinea pigs lie flat?

If you peek inside your guinea pig’s cage and see that they are lying flat on the floor, you must be wondering why they are doing this.

Most of the time, guinea pigs will lie flat and stretched out when they are comfortable.

This usually only happens once they have become accustomed to you and their surroundings.

Guinea pigs are prey animals by nature, which means they often get scared.

But if you see your guinea pigs lying flat in their cage, it means they are not much scared at the moment and want to relax.

It’s actually really good to see them lying flat while you’re in the same room because that means they’re comfortable when you’re around, or at least starting to be comfortable.

How normal is it for a guinea pig to lie flat?

When you see your guinea pigs lying flat, just know that this is perfectly normal behavior for them.

Most, if not all, pet guinea pigs will exhibit this behavior from time to time when they feel it is safe enough to do so.

In fact, it’s normal for them to do this several times a day when they feel comfortable enough.

Sometimes they even lie flat for a long time and that’s perfectly normal too.

That just means they’re comfortable enough to lay flat and vulnerable.

What does it mean when a guinea pig lies flat?

As I said before, when a guinea pig lays flat on the ground it means that it is comfortable in its environment and feels safe enough in it.

Some other reasons guinea pigs lie flat include:

you want to sleep

You try to relax.

You want to rest for a while.

So if your guinea pig feels safe enough to lie down and rest, to sleep, or to sleep on top of you, then you should let them do so without disturbing them.

They enjoy themselves, so let them relax and have fun in these peaceful moments.

Eventually they will get up and return to some of their other normal activities.

Should you be concerned if your guinea pig lies flat?

So it’s normal for guinea pigs to lie flat, but should you be concerned if they do that all the time?

If your guinea pigs are healthy and doing this consistently, there is no need to worry.

Try not to disturb them too much when they are lying flat and let them enjoy a peaceful moment to themselves.

So in general you shouldn’t worry if your guinea pigs are lying flat, but are there times when you should be concerned?

When Should You Worry If Your Guinea Pigs Are Laying Flat?

If you see your guinea pigs lying flat that’s usually good, but there are times when that’s not the case and you need to intervene. Some of these situations are:

If they don’t keep up with their regular diet.

If your sleeping patterns have changed.

If you notice physical injuries.

If you notice that your guinea pig is not consistently keeping up with its regular diet and is laying flat on the floor, it could mean something is wrong with it.

Anytime a guinea pig isn’t eating and drinking as much as it normally would, it could mean it has health problems.

If you combine that with lying flat on the ground, something could be seriously wrong.

If that’s the case, take your guinea pig to the vet so they can help you determine the cause.

Another situation to watch out for is when they don’t sleep as much or in their normal spot but lie flat in other parts of their cage.

This may mean that they are not as comfortable with their current sleeping arrangements.

If this is the case, try getting a larger cage or hutch for them to sleep in to make them more comfortable.

Another reason to be concerned is if they are lying flat and you notice physical injuries. If they do and have physical injuries, you need to take them to the vet and help them recover.

Recommendation: Why does my guinea pig lie down so much?

Where in their cage is it normal for guinea pigs to lie flat?

It is normal for guinea pigs to lie flat in their cage almost everywhere.

Most often they lie in a random spot for a while and then get up and lie flat somewhere else.

However, sometimes a guinea pig will find a certain spot that it likes to lie down in.

When they find that area, you’ll find that most of the time they just lie flat in that one spot.

However, from time to time they try other places where they want to lie down.

So if you notice that your guinea pigs seem to be lying flat in their cage all the time, don’t worry about it too much. It means they are comfortable and just enjoying a peaceful moment to themselves.

We have shown that the cerebral vasculature can be occluded by intra-arterial injection of thrombin proximal to the rete mirabile. It challenged a long-standing paradigm that stroke in pigs cannot be induced using an endovascular approach. Initially, there was great uncertainty as to whether perfusion blockage in rete, cerebral vessels would occur or not occur at all. To address this issue, we leveraged our previously established interventional MRI approaches, which have proven excellent for monitoring intra-arterial targeting20. With this approach, we were able to see in real time during the procedure if and when cerebral vessels were blocked. The addition of gadolinium-based contrast agent to thrombin facilitated dynamic imaging and visualization of thrombus formation, which was evidenced by the persistence of a hypointense signal after the infusion was complete. The position of the thrombus was then confirmed using a high-resolution SWI sequence. Thrombin/Gd solution infused at a constant rate was cleared from the vasculature and the pulsatile infusion induced coagulation more effectively. MR imaging after thrombin injection showed early changes in ADC, shortly after clot induction. Using this image-guided approach, we were able to induce ischemia with high reproducibility. Our model has unique features and an advantage over existing craniotomy-based models of ischemic stroke. Bone removal and rupture of the dura mater affect intracranial pressure, lead to loss of cerebrospinal fluid, and increase the risk of infection. Animals post-surgical stroke often require critical care for symptoms other than stroke-related neurological deficits21. Our method is relatively short, minimally invasive, precludes extensive non-stroke morbidity due to the surgical procedure, and as such improves clinical relevance. The time from skin incision to placement of the microcatheter in the ascending pharyngeal artery was less than one hour. The duration of the entire procedure was no more than 4 hours. The ischemic region was typically quite large and, as expected, this is associated with a relatively high mortality. This level of mortality may be associated with edema and herniation, as evidenced by longitudinal cerebral fissure displacement 24 h after stroke induction (shown in Fig. 2). Mortality in craniectomy-based models is lower because trepanation mitigates the effects of intracranial pressure spikes, but as such removes the clinical relevance of surgical models. In our study, two out of nine pigs developed severe morbidity after ischemia and died within 24 h. Another animal was in relatively good condition at 24 h but died during the subsequent MRI scan due to post-anaesthesia respiratory depression. This approximately 33% mortality is comparable to that observed in surgical models or with rodent MCAO models22,23,24. This relatively high mortality rate could potentially be reduced in the future by using a lower concentration or a reduced volume of intra-arterially injected thrombin.

Sheep and pigs mostly use craniotomy and craniectomy to induce stroke16,25,26. Few models of stroke exist using non-human primates, dogs, sheep, or even pigs. The use of non-human primates is considered controversial and impractical in many countries due to restricted laws. However, there are few models of ischemia in NHP27,28.

In addition to rodents, endovascular models of stroke have also been described in rabbits29, dogs30 and primates31, all of which are characterized by a favorable human-like cerebral vasculature. There have also been attempts to perform endovascular procedures in pigs19, but these have been complicated by vascular rete. Jahan et al.29 developed selective middle cerebral artery (MCA) occlusion in rabbits using a similar approach. They injected thrombin mixed with rabbit brain thromboplastin directly into the middle cerebral artery (MCA). MCA occlusion was achieved as confirmed by angiography. Jahan et al.29 did not assess whether the procedure results in ischemia, but they used this model to demonstrate pharmacological thrombolysis using intra-arterially administered plasmin. In dogs with much larger arteries, there is more flexibility in navigating the catheter, and two ways to occlude the canine MCA have been reported with access via the internal carotid artery32 or via the vertebral artery (VA)33. Stroke volume in dogs with ICA emboli injection varies with clot size and was greatest in the 1.4mm/1.7mm clot group combined with additional temporary ipsilateral ICA occlusion (4173.23 ± 603.22 mm3 )14.32. Despite the collateralization of blood vessels within the rete mirabile in pigs or sheep, there have been few attempts to direct embolic material beyond the rete mirabile. Ringer et al.19 showed that autologous thrombus was injected into the ascending pharyngeal artery. They angiographically confirmed closure of APA; However, they did not perform confirmation of ischemic injury, which is unlikely given the contralateral contribution. Gralla34 used pigs as a model for mechanical thrombectomy in acute stroke. In this case, they injected a clot into the maxillary artery (MA), resulting in a far distal obstruction, and tested the feasibility of clot removal with a clot removal device. Recent analysis by Herrmann et al.35 showed that only 2.7% of the analyzed large animal studies used a follow-up period of up to 1 week and 36.5% used a follow-up period of 3 to 6 months. Only 6.9% of studies were conducted in large animals using MRI to monitor model performance. Our entire study was guided with imaging to ensure precision, including navigating the catheter under the C-arm followed by MRI guidance to observe clot formation and stroke evolution over time. We observed the animals for up to 3 months. Important advantages of our endovascular stroke model compared to other reported large animal models include the minimally invasive approach, assessment of the very early stroke-related tissue changes with imaging, and the potential to utilize IA catheter placement for local delivery of adjuvant therapies, including stem cells36. The last feature is very attractive in the age of increasing use of thrombectomy37. We observed a fairly large range of stroke lesion sizes with a mean infarct volume of 7.39 ± 5.41. However, this variability is consistent with clinically observed stroke as well as other swine studies38 showing mean lesion volumes of 18.25 ± 12.02 cm3.

We have performed a long-term assessment of BBB status and our IF data clearly indicate chronic-stage BBB disruption. This sustained BBB opening is likely associated with and contributes to progressive neuroinflammation, degeneration, and astrocytic scarring. This could be an important therapeutic goal as some long-term patient follow-up studies report opening of the BBB up to 90 days after ischemic stroke39.

Rodents remain the most widely used approach to study stroke11 and to determine the effectiveness of various drug therapies. However, the inadequacy of these preclinical models has been considered to be the main reason for the unsuccessful translation of experimental stroke therapies into the clinic12. An example of this discrepancy is cell transplantation approaches. Preclinical rodent experiments often show significant functional recovery and reduction in MCAO lesion volume, such as B. after intravenous injection of MSCs40,41. However, clinical trials following these protocols show only marginal or no benefit42,43 The issue of animal model adequacy has been addressed by the Stroke Treatment Academic Industry Roundtable (STAIR) Committee by publishing its recommendations. According to these recommendations, preclinical studies should be conducted using animal models mimicking clinical ischemic stroke, and the efficacy and safety of the tested therapy should be verified in at least two types. Due to ease of use, rodents can be used for initial screening, with strong recommendation for validation in large animal models12.

There are some limitations of this study. First, we focused here on the feasibility of inducing cerebral ischemia without reperfusion. Further studies are needed on the extent of reperfusion and whether this model is suitable for inducing pharmacological thrombolysis by the intra-arterial or intravenous route. However, we anticipate that pharmacological thrombolysis will be effective in this model since freshly induced thrombi should be easier to lyse compared to better organized thrombotic material detached from distant sites. Studies of reperfusion in this model will be important, particularly given the growing role of mechanical endovascular thrombectomy and the prospect of using intra-arterial adjuvant treatments after reperfusion. On the other hand, a meta-analysis by Cui et al.44 showed the need for clinically relevant models of permanent occlusion. Second, this study was conducted on young animals because mature or aging pigs are difficult to handle in such a study. Using older mini pigs could be a good solution. Access to advanced imaging equipment and neuroradiological expertise can be a limitation; However, as interest in endovascular stroke treatment grows, access to infrastructure and expertise is improving. Third, this study was conducted on a relatively small group of animals. We were able to demonstrate with this number of animals how the rete mirabile challenge for stroke induction can be met, but obviously further testing is needed to assess the feasibility, reproducibility, and usefulness of the model for studies of reperfusion and novel therapeutic approaches to confirm.

In conclusion, this study has provided for the first time the feasibility of inducing an endovascular stroke model in pigs. We could observe in real time the formation of a thrombin-induced clot and the resulting blockage of cerebral perfusion and finally a stroke lesion. Our model generated a relatively large infarct volume covering most of the MCA territory. Overall, we have established a new model of ischemic stroke in pigs with high clinical relevance. The model will contribute to studies aimed at understanding the pathophysiology of stroke and, more importantly, the development of new drugs.

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A recent case of mine involved a middle-aged male guinea pig. He had a severe head tilt to the left. He was unable to hold his head in a normal position. He was even so far that he fell and rolled over. He hadn’t been able to eat his guinea pig chow

for the last few days. Head tilt is a common problem in rabbits but a very rare condition in guinea pigs. In addition, the guinea pig had a skin mite problem.

In guinea pigs, severe head tilt can result from an ear infection that spreads to the middle ear and inner ear. This type of infection causes head tilt (torticollis), often referred to as “wry neck” in rabbits. It also causes loss of balance and nausea.

Middle and inner ear infections require long-term use of an antibiotic. Guinea pigs (and hamsters) are very susceptible to side effects, including death, from many of the commonly used antibiotics, such as amoxicillin, penicillin, clindamycin, and erythromycin. Fortunately, they tolerate Baytril (enrofloxacin) very well. This guinea pig was given Baytril orally using Baytril ear drops to be placed in the ear. In order to improve its appetite, this guinea pig was fed an intensive feed that can be fed through a syringe. This helps prevent problems with his digestive system from developing if he doesn’t eat normally.

Skin parasites are very common in guinea pigs. Guinea pigs often have mites and lice. Occasionally, guinea pigs also have fleas, especially if dogs and/or cats live in the same house. Skin mites can cause serious problems in guinea pigs, including seizures and even death in severe cases. Luckily, skin mites are easy to treat with Ivermectin or Revolution. In this case, Revolution was selected to treat the guinea pig’s mites.

From: Dr. Jerry Murray

Featured Image: Via Pezibear/Pixabay