Cerebral Blood Flow and Edema in Perinatal Hypoxic-Ischemic Brain Damage

Abstract

The relationship between cerebral blood flow (CBF) and the evolution of brain edema was investigated in an experimental model of perinatal hypoxic-ischemic brain damage. Seven-d postnatal rats were subjected to unilateral common carotid artery ligation followed by 3 h of hypoxia with 8% oxygen at 37 degrees C. This insult produces neuronal necrosis and/or infarction only in the cerebral hemisphere ipsilateral to the arterial occlusion in the majority of animals; hypoxia alone produces no damage. CBF, measured by the indicator diffusion technique using iodo[14C]-antipyrine, and tissue water content were determined concurrently in both cerebral hemispheres at specific intervals during recovery from cerebral hypoxia-ischemia. Water contents in the ipsilateral cerebral hemisphere were 89.1, 89.6, 89.7, 91.0, and 88.3% at 30 min, 4 h, 24 h, 3 d, and 6 d, respectively (p less than 0.001); whereas the percent tissue water in the contralateral hemisphere was unchanged from values in nonligated, hypoxic control rats (87.7%). CBF was similar in both cerebral hemispheres at 30 min, 4 h, and 24 h of recovery (50-65 mL/100 g/min) and not different from age-matched controls. At 3 and 6 d, CBF in the ipsilateral cerebral hemisphere was 30 and 26% of the contralateral hemisphere and 23 and 29% of the control animals, respectively (p less than 0.001). No inverse correlation existed between the changes in brain water content and CBF at any interval until 6 d of recovery. Thus, an early hypoperfusion does not follow perinatal cerebral hypoxia-ischemia, as occurs in adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Deleterious Effects of Plasminogen Activators in Neonatal Cerebral Hypoxia-Ischemia

“…However, at 4 hours of recovery, the patches of vascular obstructions disappeared, and the cerebral perfusion index rose to 74% of the contralateral side (P ϭ 0.03, n ϭ 8) (Figure 1, C, D, and Q). These results confirmed the previous report, 21 indicating that HI only causes a brief period of vascular obstruction in the newborn brain. The HI-induced transient hypoperfusion in newborn brains is in contrast to its effect of persistent deficits of cerebral perfusion in adult brains.…”

“…21 To confirm this observation, we used fluorescein-conjugated dextran (FITC-dextran) as a tracer of blood perfusion to examine the brains of 7-dayold rat pups at 1 and 4 hours after the Vannucci model of HI. 2 This analysis revealed patches of vascular obstruction in the hippocampus and the cerebral cortex on the carotid-occluded side of brain at 1 hour of recovery (Figure 1, A and B).…”

“…The present study was stimulated by our recent publication showing while HI only transiently impairs cerebral perfusion in newborns, 21 it produces persistent occlusive fibrin deposition in adult brains. 22 In light of the contrasting effects of HI in newborn versus adult brains, we hypothesized that neonatal brains have an age-specific response to HI through activation of the endogenous plasminogen system.…”

Glial activation in white matter following ischemia in the neonatal P7 rat brain

“…This reperfusion has been detected before brain infarction was visible (pale zone). Indeed, first signs of cell death appear in a few scattered TUNEL-positive nuclei in the fronto-parietal cortex at 4-6 hours of recovery with a maximum of cell death occurring between 24 and 96 hours (Mujsce et al, 1990).…”

Dynamic Spatio-Temporal Imaging of Early Reflow in a Neonatal Rat Stroke Model

“…7 Brain tissue perfusion has also been quantified by autoradiography in the P7 hypoxic-ischemic rat, and showed CBF in the opposite cortex remained at normal levels despite a 'hypoxia only' insult, whereas flow to the brainstem and cerebellum nearly doubled or tripled after hypoxia-ischemia (HI) in rat, respectively. [8][9][10] Conflicting data were reported using laser-Doppler flowmetry under normoxic resuscitation after HI in rat with increased, 11 decreased 12 and none modifications 13 of regional CBF. More recently, the spatial and temporal profiles of cortical surface CBF were analyzed in P8 mouse and P7 rat pups subjected to HI using laser speckle imaging.…”