BackgroundIn dogs with ischaemic stroke, a very common site of infarction is the cerebellum. The aim of this study was to characterise neurological signs in relation to infarct topography in dogs with suspected cerebellar ischaemic stroke and to report short-term outcome confined to the hospitalisation period. A retrospective multicentre study of dogs with suspected cerebellar ischaemic stroke examined from 2010–2015 at five veterinary referral hospitals was performed. Findings from clinical, neurological, and paraclinical investigations including magnetic resonance imaging were assessed.ResultsTwenty-three dogs, 13 females and 10 males with a median age of 8 years and 8 months, were included in the study. The Cavalier King Charles Spaniel (n = 9) was a commonly represented breed. All ischaemic strokes were located to the vascular territory of the rostral cerebellar artery including four extensive and 19 limited occlusions. The most prominent neurological deficits were gait abnormalities (ataxia with hypermetria n = 11, ataxia without hypermetria n = 4, non-ambulatory n = 6), head tilt (n = 13), nystagmus (n = 8), decreased menace response (n = 7), postural reaction deficits (n = 7), and proprioceptive deficits (n = 5). Neurological signs appeared irrespective of the infarct being classified as extensive or limited. All dogs survived and were discharged within 1–10 days of hospitalisation.ConclusionsDogs affected by rostral cerebellar ischaemic stroke typically present with a collection of neurological deficits characterised by ataxia, head tilt, and nystagmus irrespective of the specific cerebellar infarct topography. In dogs with peracute to acute onset of these neurological deficits, cerebellar ischaemic stroke should be considered an important differential diagnosis, and neuroimaging investigations are indicated. Although dogs are often severely compromised at presentation, short-term prognosis is excellent and rapid clinical improvement may be observed within the first week following the ischaemic stroke.
BackgroundDogs develop spontaneous ischaemic stroke with a clinical picture closely resembling human ischaemic stroke patients. Animal stroke models have been developed, but it has proved difficult to translate results obtained from such models into successful therapeutic strategies in human stroke patients. In order to face this apparent translational gap within stroke research, dogs with ischaemic stroke constitute an opportunity to study the neuropathology of ischaemic stroke in an animal species.Case presentationA 7 years and 8 months old female neutered Rottweiler dog suffered a middle cerebral artery infarct and was euthanized 3 days after onset of neurological signs. The brain was subjected to histopathology and immunohistochemistry. Neuropathological changes were characterised by a pan-necrotic infarct surrounded by peri-infarct injured neurons and reactive microglia/macrophages and astrocytes.ConclusionsThe neuropathological changes reported in the present study were similar to findings in human patients with ischaemic stroke. The dog with spontaneous ischaemic stroke is of interest as a complementary spontaneous animal model for further neuropathological studies.
Objectives: To investigate dogs with acute onset of intracranial signs suspected of stroke by primary veterinary clinicians, and establish possible differential diagnoses and long-term outcome. In addition, serum C-reactive protein and plasma cytokines were investigated as potential biomarkers of disease.Materials and MethOds: All cases were evaluated by neurologic examination, routine haematology and biochemistry and measurement of serum C-reactive protein, plasma cytokine concentrations (interleukin-2, -6, -8, -10, tumour necrosis factor) and low-field MRI.results: Primary veterinarians contacted the investigators with 85 suspected stroke cases. Only 20 met the inclusion criteria. Of these, two were diagnosed with ischaemic stroke. Other causes were idiopathic vestibular syndrome (n=6), brain tumour (n=5) and inflammatory brain disease (n=2); in five cases a precise diagnosis could not be determined. Median survival times were: brain tumour, 3 days, idiopathic vestibular syndrome, 315 days, ischaemic stroke, 365 days and inflammatory central nervous system (CNS) disease, 468 days. The median plasma concentrations of interleukin-2, -6, -8, -10 or tumour necrosis factor were not significantly increased in any of the diagnosis groups compared to healthy controls. Serum C-reactive protein was higher in dogs with brain tumours and inflammatory brain disease but not above the upper bound of the reference interval.clinical significance: Dogs that present with acute onset intracranial disease may have ischaemic stroke but are more likely to have other causes. Many dogs with such acute onset of neurological dysfunction (brain tumours excluded) may recover within a couple of weeks despite their initial severe clinical appearance. a These authors shared first authorship.
Inflammatory cytokines are potential modulators of infarct progression in acute ischaemic stroke, and are therefore possible targets for future treatment strategies. Cytokine studies in animal models of surgically induced stroke may, however, be influenced by the fact that the surgical intervention itself contributes towards the cytokine response. Community-dwelling domestic dogs suffer from spontaneous ischaemic stroke, and therefore, offer the opportunity to study the cytokine response in a noninvasive set-up. The aims of this study were to investigate cytokine concentrations in plasma and cerebrospinal fluid (CSF) in dogs with acute ischaemic stroke and to search for correlations between infarct volume and cytokine concentrations. Blood and CSF were collected from dogs less than 72 h after a spontaneous ischaemic stroke. Infarct volumes were estimated on MRIs. Interleukin (IL)-2, IL-6, IL-8, IL-10 and tumour necrosis factor in the plasma, CSF and brain homogenates were measured using a canine-specific multiplex immunoassay. IL-6 was significantly increased in plasma (P=0.04) and CSF (P=0.04) in stroke dogs compared with healthy controls. The concentrations of other cytokines, such as tumour necrosis factor and IL-2, were unchanged. Plasma IL-8 levels correlated significantly with infarct volume (Spearman’s r=0.8, P=0.013). The findings showed increased concentrations of IL-6 in the plasma and CSF of dogs with acute ischaemic stroke comparable to humans. We believe that dogs with spontaneous stroke offer a unique, noninvasive means of studying the inflammatory processes that accompany stroke while reducing confounds that are unavoidable in experimental models.
Domestic dogs are superior models for translational medicine due to greater anatomical and physiological similarities with humans than rodents, including hereditary diseases with human equivalents. Particularly with respect to neurodegenerative medicine, dogs can serve as a natural, more relevant model of human disease compared to transgenic rodents. Herein we report attempts to develop a canine-derived in vitro model for neurodegenerative diseases through the generation of induced pluripotent stem cells from a 14-year, 9-month-old female West Highland white terrier with mild cognitive impairment (MCI). Canine induced pluripotent stem cells-like cells (ciPSCLC) were generated using human OSKM and characterized by positive expression of pluripotency markers. Due to inefficient viral vector silencing we refer to them as ciPSCLCs. Subsequently, the ciPSCLC were subjected to neural induction according to two protocols both yielding canine neural progenitor cells (cNPCs), which expressed typical NPC markers. The cNPCs were cultured in neuron differentiation media for 3 weeks, resulting in the derivation of morphologically impaired neurons as compared to iPSC-derived human counterparts generated in parallel. The apparent differences encountered in this study regarding the neural differentiation potential of ciPSCLC reveals challenges and new perspectives to consider before using the canine model in translational neurological studies.
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