Abstract
Background: Stroke is the first cause of disability in adults in western countries. Infarct of the internal capsule (IC) may be related to motor impairment and poor prognosis in stroke patients. Functional deficits due to medium-sized infarcts are difficult to predict, except if the specific site of the lesion is taken into account. None of the few pre-clinical models recapitulating this type of stroke has shown clear, reproducible, and long-lasting sensorimotor deficits. Here, we developed a rat model of lacunar infarction within the IC, key structure of the sensorimotor pathways, by precise injection of malonate.Methods: The mitochondrial toxin malonate was injected during stereotactic surgery into the IC of rat brains. Rats were divided in three groups: two groups received malonate solution at 1.5M (n = 12) or at 3M (n = 10) and a sham group (n = 5) received PBS. Three key motor functions usually evaluated following cerebral lesion in the clinic strength, target reaching, and fine dexterity were assessed in rats by a forelimb grip strength test, a skilled reaching task (staircase) for reaching and dexterity, and single pellet retrieval task. Sensorimotor functions were evaluated by a neurological scale. Live brain imaging, using magnetic resonance (MRI), and post-mortem immunohistochemistry in brain slices were performed to characterize the lesion site after malonate injection.Results: Intracerebral injection of malonate produced a 100% success rate in inducing a lesion in the IC. All rats receiving the toxin, regardless the dose injected, had similar deficits in strength and dexterity of the contralateral forepaw, and showed significant neurological impairment. Additionally, only partial recovery was observed with respect to strength, while no recovery was observed for dexterity and neurological deficit. MRI and immunostaining show volume size and precise location of the lesion in the IC, destruction of axonal structures and Wallerian degeneration of fibers in the area above the injection site.Conclusions: This pre-clinical model of lacunar stroke induces a lesion in the IC with measurable and reproducible sensorimotor deficits, and limited recovery with stabilization of performance 2 weeks post-injury. Future therapies in stroke may be successfully tested in this model.
Highlights
Ischemic stroke is a devastating disease, being the major cause of acquired disabilities in adults and the second cause of dementia, after Alzheimer disease [1]
Functional magnetic resonance imaging (MRI) studies in stroke patients have shown that total infarct of the internal capsule (IC) has a negative clinical prognosis and is related to motor impairment
Rats receiving the high dose of ET-1 (n = 4) could not be followed because of the 100% mortality rate observed after injection in the IC
Summary
Ischemic stroke is a devastating disease, being the major cause of acquired disabilities in adults and the second cause of dementia, after Alzheimer disease [1]. Despite the wide use of ET-1, this model has a few limitations, i.e., the high mortality rate [14, 15], the only partial destruction of IC fibers and the lack of marked sensorimotor deficits [11]. Another pre-clinical model of IC stroke uses electrocoagulation of the anterior choroidal artery [16, 17]. This model has limitations related to the delicate surgery It does not always induce volume size-reproducible lesions, because of the variability in vasculature and collateral blood flow, and the motor impairment is not long-lasting [16,17,18]. We developed a rat model of lacunar infarction within the IC, key structure of the sensorimotor pathways, by precise injection of malonate
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
