Evolution of brain injury after transient middle cerebral artery occlusionin neonatal rats

Background and Purpose-Stroke in preterm and term babies is common and resu lts in significant morbidity. The vulnerability and pathophysiorogical mech anisms of neonatal cerebral ischemia-reperfusion may differ from those in t he mature cerebral nervous system because of the immaturity of many recepto r systems and differences in metabolism in neonatal brain. This study detai ls the neuropathological sequelae of reperfusion-induced brain injury after transient middle cerebral artery (MCA) occlusion in the postnatal day 7 (P 7) rat. Methods-P7 rats were subjected to 3 hours of MCA occlusion followed by repe rfusion or sham surgery. Diffusion-weighted MRT was performed during MCA oc clusion, and maps of the apparent diffusion coefficient (ADC) were construc ted. Contrast-enhanced MRT was performed in a subset of animals before and 20 minutes after reperfusion. Triphenyltetrazolium chloride (TTC) staining of the brain was performed 24 hours after reperfusion. Immunohistochemistry to identify astrocytes (glial fibrillary acidic protein), reactive microgl ia (ED-1), and neurons (microtubule-associated protein 2) and cresyl violet staining were done 4, 8, 24, and 72 hours after reperfusion. Results-On contrast-enhanced MRI, nearly complete disruption of cerebral bl ood flow was evident in the vascular territory of the MCA during occlusion. Partial. restoration of blood flow occurred after removal of the suture. A significant decrease of the ADC, indicative of early cytotoxic edema, occu rred in anatomic regions with a disrupted blood supply. The decline in ADC was associated with TTC- and cresyl violet-determined brain injury in these regions 24 hours later. The ischemic core was rapidly infiltrated with rea ctive microglia and was surrounded by reactive astroglia. Conclusions-In P7 rats, transient MCA occlusion causes acute cytotoxic edem a and severe unilateral brain injury. The presence of a prominent inflammat ory response suggests that both the ischemic episode and the reperfusion co ntribute to the neuropathological outcome.