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Animal models of transient ischemic attack: a review.

ABSTRACT: Transient ischemic attack (TIA) is defined as a brief episode of neurological dysfunction caused by focal cerebral ischemia. TIA is a critical early warning signal of stroke. Patients with TIA may have long-term cognitive decline. The pathogenesis and pathological changes of TIA have not been fully elucidated. Animal models can simulate the process of human diseases and are essential tools to investigate injury mechanisms and therapeutic approaches of TIA. Most TIA animal models are based on ischemic stroke models and the definition of TIA. Each model has unique strengths and weaknesses. The establishment of a successful and reliable TIA model should follow three criteria: (1) objective evidence of cerebral arteries occlusion and reperfusion, (2) no permanent neurological deficit, and (3) no acute cerebral infarction. However, experimental animal models are impossible to be completely consistent with human TIA, because TIA itself is a heterogeneous disease. In the present review, the selection of animals, methodological development, and evaluation of cerebral blood flow of animal models of TIA are comprehensively evaluated.

SUBMITTER: Wang J

PROVIDER: S-EPMC7083805 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Animal models of transient ischemic attack: a review.

Wang Jiahui J Zhang Ping P Tang Zhouping Z

Acta neurologica Belgica 20200211 2

Transient ischemic attack (TIA) is defined as a brief episode of neurological dysfunction caused by focal cerebral ischemia. TIA is a critical early warning signal of stroke. Patients with TIA may have long-term cognitive decline. The pathogenesis and pathological changes of TIA have not been fully elucidated. Animal models can simulate the process of human diseases and are essential tools to investigate injury mechanisms and therapeutic approaches of TIA. Most TIA animal models are based on isc ...[more]

PMID: 32048230

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Project description:BackgroundIdentifying and treating patients with transient ischemic attack is an effective means of preventing stroke. However, making this diagnosis can be challenging, and over a third of patients referred to stroke prevention clinic are ultimately found to have alternate diagnoses.AimsWe performed a systematic review to determine how neurologists diagnose transient ischemic attack.Summary of reviewA systematic literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using MEDLINE, Embase, and the Cochrane Library databases. Publications eligible for inclusion were those that included information on the demographic or clinical features neurologists use to diagnose transient ischemic attacks or transient ischemic attack-mimics. Of 1666 citations, 210 abstracts were selected for full-text screening and 80 publications were ultimately deemed eligible for inclusion. Neurologists were more likely to diagnose transient ischemic attack based on clinical features including negative symptoms or speech deficits. Patients with positive symptoms, altered level of consciousness, or the presence of nonfocal symptoms such as confusion or amnesia were more likely to be diagnosed with transient ischemic attack-mimic. Neurologists commonly include mode of onset (i.e. sudden versus gradual), recurrence of attacks, and localizability of symptoms to a distinct vascular territory in the diagnostic decision-making process. Transient ischemic attack diagnosis was more commonly associated with advanced age, preexisting hypertension, atrial fibrillation, and other vascular risk factors.ConclusionsNeurologists rely on certain clinical and demographic features to distinguish transient ischemic attacks from mimics, which are not currently reflected in widely used risk scores. Clarifying how neurologists diagnose transient ischemic attack may help frontline clinicians to better select patients for referral to stroke prevention clinics.

Project description:BackgroundPatients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease.MethodsIn this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction.ResultsBy 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003).ConclusionsIn this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).

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Animal models of transient ischemic attack: a review.

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Animal models of transient ischemic attack: a review.

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