Agonists of glutamate ionotropic (NMDA) and metabotropic receptors (mGluRI and mGluRIII) had the regulatory effect on ADP-ribosyl cyclase/CD38 activity in cerebellar granular cells of newborn rats. Perinatal hypoxic-ischemic brain injury was followed by dysregulation of this mechanism.

We have studied CD38 expression in rat brain after perinatal hypoxic-ischemic injury. We found regulation of CD38 by modulators of metabolism of endogenous retinoic acid or by exogenous retinoic acid. Possibility to use the data for development of pharmacological method of neuroprotection is discussed.

Objective: to study the mechanism that is responsible for impaired neuronal cell electroexcitability and viability, which is associated with modification of ADP-ribosyl cyclase in cerebral ischemic lesion, as well as the possibilities of pathogenet-ically correcting these disorders. Materials and methods. Acute cerebral ischemia was simulated in vivo on noninbred albino male rats, by ligating the right common carotid artery under general anesthesia. y-Interferon was intraperitoneally administered to the mammal in a dose of 5000 IU/kg body weight once daily for 3 days until unilateral extravasal occlusion of the common carotid artery occurred. The activity of ADP-ribosyl cyclase was evaluated by the fluorometric technique. CD38 expression in the brain cells was immunohistohemically detected. The severity of neurological symptoms was evaluated using the international NSS scale for laboratory animals. Cognitive dysfunction was recorded employing the standard test — the Morris water maze. The validity of differences was assessed by Student’s t-test and T-test, by applying STATISTICA version 6.0 (StatSoft-Russia, 1999) and BIOSTATISTICA programs. Results. Progressive neurological and cognitive deficit-induced changes occurred in the activity and expression of ADP-ribosyl cyclase/CD38 in the neuronal and glial cells in the course of brain ischemia. Neuroprotection and prevention of postischemic cognitive dysfunction were achieved by the use of y-interferon as a modifier of the brain cell expression of CD38/ADP-ribosyl cyclase.