REDUCTION IN CEREBRAL ISCHEMIC-INJURY IN THE NEWBORN RAT BY POTENTIATION OF ENDOGENOUS ADENOSINE

Because of ontogenic influences on the pathophysiologic mechanisms of brain injury in the perinatal brain, and in particular, the incomplete development of adenosine receptor systems, we investigated the potent ial for adenosine to provide cerebroprotection in a well established n ewborn rat model of hypoxia-ischemia. Fifteen litters of postnatal d 7 animals were subjected to unilateral carotid ligation and exposure to hypoxia (8% oxygen) for 3 h. Immediately after hypoxia-ischemia, anim als received either the adenosine deaminase inhibitor deoxycoformycin (DCF; 2.5 mg/kg intraperitoneally) or the adenosine uptake inhibitor p ropentofylline (PPF; 10 mg/kg intraperitoneally); paired littermates r eceived an equivalent volume of normal saline. On postnatal d 14, inju ry or protection was assessed by differences in hemispheric weights, m orphometric determinations of infarct area, and histopathologic analys es. DCF resulted in a 34% (p = 0.02) and 31% (p = 0.03) reduction in h emispheric weight disparities and infarct area, respectively; for PPF, these reductions were 46% (p = 0.03) and 32% (p = 0.04), respectively . Light microscopic examinations of striatum, thalamus, hippocampus, a nd cortex revealed that both drugs significantly improved histologic s cores as well. Measurements in six separate litters indicated that nei ther drug significantly reduced core body temperature for at least 6 h postadministration. These findings indicate that potentiation of endo genous adenosine levels in the perinatal brain can significantly ameli orate brain injury. Each of these treatment strategies was effective e ven when administered after the hypoxic-ischemic insult. Thus, further investigations of adenosinergic therapies are warranted in this and o ther perinatal models of cerebral ischemia to elucidate in detail thei r potential for clinical application.