Evidence that disruption of the blood-brain barrier precedes reduction in cerebral blood flow in hypertensive encephalopathy.

Alternative hypotheses concerning the pathogenesis of hypertensive encephalopathy are that vasospasm produces cerebral ischemia and cerebral edema, or that passive dilation of cerebral vessels during severe hypertension produces disruption of the blood-brain barrier and cerebral edema. Stroke-prone spontaneously hypertensive rats (SHRSP) were studied when they developed signs of neurological dysfunction. We measured regional cerebral blood flow (rCBF) with 14C-iodoantipyrine, and permeability of the blood-brain barrier with Evans blue dye. Twelve rats had focal disruption of the barrier without histological evidence of ischemic infarction or cerebral hemorrhage: areas with disruption of the barrier had severe focal edema in seven rats and minimal edema in five rats. In areas with disruption of the barrier and marked focal edema, rCBF was decreased to 38 +/- 8 (mean +/- SE) ml/min/100 g vs 102 +/- 13 (p less than 0.05) in other areas of the ipsilateral hemisphere, and 86 +/- 16 in the homologous area of the contralateral hemisphere (p less than 0.05). In contrast, in areas with disruption of the blood-brain barrier with only minimal edema, rCBF was normal or increased: rCBF was 100 +/- 11 ml/min/100 g vs 85 +/- 12 in other areas of the ipsilateral hemisphere (p greater than 0.05) and 64 +/- 8 in the homologous area contralaterally (p less than 0.05). The findings indicate that edema precedes reduction in rCBF in SHRSP and suggest that the initiating event in hypertensive encephalopathy is disruption of the blood-brain barrier, and not vasospasm.