Beagle puppy model of perinatal cerebral infarction

Abstract

Asphyxia, with its attendant hypotension, is by far the most common cause of neonatal cerebral infarction and frequently results in lesions of the parieto-occipital white matter. This study examines the effects of hypotension on regional cerebral blood flow (CBF), local cerebral glucose utilization (LCGU), and serum prostaglandin levels in newborn beagle pups. The animals (24 to 96 hours old) were anesthetized, tracheotomized, and paralyzed. Pups were randomly divided into two groups: one was subjected to hemorrhagic hypotension and the other received no insult. Hypotension was induced by slow venous hemorrhage to maintain a mean arterial blood pressure of 20 to 30 mm Hg. Autoradiographic determinations of LCGU using carbon-14 (14C)-2-deoxyglucose were performed 45 minutes after randomization to groups. Autoradiographic determinations of CBF were performed using 14C-iodoantipyrine on a second group of pups 15 minutes after randomization. Prostaglandins were measured immediately before and 15 minutes after insult or control manipulation. There were no significant differences in the values for thromboxane B2 or 6-keto-prostaglandin F1 alpha, the stable breakdown products of thromboxane A2, and prostacyclin. Prostaglandin E2 levels significantly increased in response to hemorrhagic hypotensive insult. In addition, although regional CBF was maintained in cortical and central gray matter structures during hypotension, CBF to the periventricular temporal and parietal white matter zones significantly decreased, and LCGU was increased in these same regions during hypotensive insult. The uncoupling of CBF and metabolism in these periventricular white matter regions may be responsible for the neuropathological sequelae of perinatal asphyxia.

Elevated Diastolic Closing Margin Is Associated with Intraventricular Hemorrhage in Premature Infants

“…2,3 Hypotension and low-flow states, as well as reperfusion hyperemia after ischemia have both been implicated in the pathogenesis of IVH in both human premature infants 4–6 and in experimental animal models. 7,8 …”

The Ontogeny of Cerebrovascular Pressure Autoregulation in Premature Infants

“…4,5 From animal models, both ischemia and hyperperfusion have been implicated in the etiology of neonatal brain injury. [6][7][8][9][10][11] This apparent contradiction has caused a divergence of mechanistic understanding of intraventricular hemorrhage (IVH), which is the most common and easily detectable of all neonatal neurologic injuries. Does the fragile vascular bed of the germinal matrix bleed from ischemia followed by reperfusion or from hyperemia driven by excessive arterial blood pressure (ABP)?…”

Vasoconstriction in Telencephalic Microvessels: A Response to One Model for Intraventricular Hemorrhage in Beagle Pups

“…This study documents with ultrastructural data and morphometry that brain microvessels are vasoconstricted 75 mintes following hemorrhagic hypotension then volume re-expansion, one of the most popular models for studying IVH (Coulter et al, 1985;Goddard-Finegold and Michael, 1984;Ment et al, 1983Ment et al, , 1984Ment et al, , 1985Pasternak et al, 1983).…”