Regional cerebral blood flow during hypoxia-ischemia in immature rats.

Abstract

Immature rats subjected to a combination of unilateral common carotid artery ligation and hypoxia sustain brain damage confined largely to the ipsilateral cerebral hemisphere. To ascertain the extent and distribution of ischemic alterations in the brains of these small animals, we modified the Sakurada technique to measure regional cerebral blood flow using carbon-14 autoradiography. Seven-day-old rats underwent right common carotid artery ligation following which they were rendered hypoxic with 8% O 2 at 37° C. Before and during hypoxia, the rat pups received an injection of iodo[ l4 C]antipyrine for determination of regional cerebral blood flow. Blood flows to individual structures of the ipsilateral cerebral hemisphere were not influenced by arterial occlusion alone; flows to the contralateral hemisphere and to the brainstem and cerebellum actually increased by 25-50%. Hypoxla-ischemia was associated with decreases in regional cerebral blood flow of the ipsilateral hemisphere such that by 2 hours, flows to subcortical white matter, neocortex, striatum, and thalamus were 15,17,34, and 41% of control, respectively. The hierarchy of the blood flow reductions correlated closely with the distribution and extent of ischemic neuronal necrosis. However, unlike the pathologic pattern of this model, the degree of ischemia appeared homogeneous within each brain region. Blood flows to contralateral cerebral hemispheric structures were relatively unchanged from prehypoxic values, whereas flows to the brainstem and cerebellum nearly doubled and tripled, respectively. Thus, ischemia is the predominant factor that determines the topography of tissue injury to major regions of immature rat brain, whereas metabolic factors (intrinsic vulnerability) may influence the heterogeneous pattern of damage seen within individual structures. (Stroke 1988; 19:245-250) A critical question in perinatal medicine is whether hypoxia alone is capable of damaging the brain of a fetus or newborn infant or whether cerebral ischemia, with or without concurrent systemic hypoxia, is necessary for tissue injury to occur. Investigations in animals suggest that hypoxia alone does not damage the immature brain and that superimposed ischemia, produced either by arterial occlusion (stroke) or by systemic hypotension, is a necessary prerequisite for tissue destruction.l~* If this observation can be extended to human infants, then hypoxemia alone should be relatively innocuous so long as the cerebral arteries remain patent and systemic hypotension is avoided.We recently developed an experimental model of perinatal hypoxic-ischemic brain damage in developing rats.3 The technique involves the ligation of one common carotid artery followed by exposure of the rat to systemic hypoxia for 2 or more hours. We assumed that the single carotid artery occlusion provided the ischemia necessary to damage the immature brain, although cerebral perfusion was not assessed directly in the original investigation. In our present study, we measured regional cerebral blood flow ...

Magnetization transfer and diffusion imaging of acute axonal damage in the cerebral peduncle following hypoxia–ischemia in neonatal rats

“…Parenchymal lesions were evident within a brain distribution consistent with the P7 model of unilateral transient cerebral hypoxia-ischemia (23,24). Cortical, striatal, and thalamic ischemic changes were observed consistently in all animals (lesion volume of 37.1 ± 7.8% of the hemisphere at 1 d after hypoxia-ischemia).…”

“…MRI changes in this model are also well characterized within the regions that develop infarcts, such as the cerebral cortex. White matter structures such as the internal capsule may also receive ischemic damage, but, of importance, posterior brainstem and pontine structures including the cerebral peduncle are not ischemic in this model (23). In ischemic damaged regions at 1 d postinsult, there are increases in T 2 associated with vasogenic edema and decreases in ADC that have been shown to be associated with a cell swelling or cytotoxic edema (25,26).…”

Vascular Response to Hypoxic Preconditioning in the Immature Brain

“…neonatal rodent model of HI, the distribution and extent of ischemic brain tissue injury is closely related to the regional reduction of CBF (Vannucci et al, 1988). Our results indicate that hypoxic PC affects the vascular response to HI, resulting in a less pronounced decrease of CBF (which may provide partial preservation of high energy phosphates during HI) and a subsequent reduction in brain damage.…”

The Instrumented Fetal Sheep as a Model of Cerebral White Matter Injury in the Premature Infant

“…The basis for this difference in susceptibility to gray matter injury in rodents relative to sheep and humans is likely to be multifactorial. The cerebrovascular supply of rodent white matter is structurally and physiologically very dissimilar to humans and sheep [55,56]. In addition, the timing of expression of the subtypes of glutamate receptors appears to differ between rodents and both humans and sheep [57][58][59], which may further contribute to the pronounced susceptibility of neonatal rodent cerebral gray matter to excitotoxic injury [60].…”