THE IMPACT OF ISCHEMIC LESION ON THE CELLULAR MICROENVIRONMENT AND LONG-TERM NEUROBEHAVIORAL OUTCOMES IN A NOVEL MURINE MODEL OF PEDIATRIC STROKE

Pediatric ischemic stroke is a cerebrovascular disease caused by cerebral artery occlusion occurring between 29 days of life and 18 years of age. Although rare, it is a major cause of mortality and long-term morbidity in children. Nevertheless, its pathophysiology remains poorly understood, mainly due to the limited availability of appropriate preclinical models.
Here, we present a novel murine model of pediatric stroke based on transient distal middle cerebral artery (dMCA) occlusion in postnatal day 14–15 mice. Following craniotomy, the dMCA was transiently compressed with a blunted capillary for 60 minutes to induce focal cortical ischemia. Model validation included infarct volume assessment using 2,3,5-triphenyltetrazolium chloride staining at 1 day post-stroke (dPS) (n=7). Neuronal, microglial, and astroglial densities were analyzed in ischemic and control regions at 1dPS using multiple fluorescent labeling (n=4 per condition). Long-term neurological outcomes were evaluated using an adapted SHIRPA battery, novel object recognition, and open field tests at baseline and at 1, 3, 7, and 14dPS (n =10 per condition).
The occlusion induced cerebral cortical infarction and neuronal loss at 1dPS, accompanied by increased astroglial and microglial surface coverage and cell density within ischemic regions. Behavioral analyses revealed mild acute sensorimotor deficits followed by progressive recovery, with subtle persistent deficits in some animals while mild cognitive impairments emerged at 14dPS.
In conclusion, this model reproduces key pathological and functional features of pediatric ischemic brain injury and represents a valuable tool for investigating early stroke-induced mechanisms.