Regulation of cerebral vasculature in normal and ischemic brain

Abstract

We outline the mechanisms currently thought to be responsible for controlling cerebral blood flow (CBF) in the physiologic state and during ischemia, focusing on the arterial pial and penetrating microcirculation. Initially, we categorize the cerebral circulation and then review the vascular anatomy. We draw attention to a number of unique features of the cerebral vasculature, which are relevant to the microcirculatory response during ischemia: arterial histology, species differences, collateral flow, the venous drainage, the blood-brain barrier, astrocytes and vascular nerves. The physiology of the arterial microcirculation is then assessed. Lastly, we review the changes during ischemia which impact on the microcirculation. Further understanding of the normal cerebrovascular anatomy and physiology as well as the pathophysiology of ischemia will allow the rational development of a pharmacologic therapy for human stroke and brain injury.

Fig 1

A. Intracerebral arterioles response to intraluminal pressure in the absence of flow (n=8). B, The change in diameter of intracerebral arterioles as a function of intraluminal flow rate at constant intravascular pressure of 60 mm Hg (n=12). Values are mean ± SEM. *P<.05, ^#P<.01 vs diameter at pressure of 20 mm Hg (left) or at flow of 0 μL/min (right), respectively (Ngai and Winn, 1995; used with permission)

Fig 2

Steady-state responses of pial arteries and arterioles to induced hypotension. Note that smaller arterioles have the most vigorous response to hypotension.(Kontos et al., 1978; used with permission)

Fig. 3

Changes in adenosine (Ado), phosphocreatine (PCr), lactate (Lac), Energy Charge (E.C.) and adenosine triphosphate (ATP) during 60 seconds of complete cerebral ischemia in rat. Note that measurable changes in adenosine and PCr occurred at 5 sec., lactate at 10 sec., energy charge at 30 sec. and ATP at 60 sec. after the onset of ischemia. Cerebral tissue obtained by freeze-blow technique. Ischemia induced by transsection of the retroperitoneal aorta with brain perfusion pressure decreasing to 0 mm Hg by ~ 0.1sec. E.C.= (ATP+0.05 ADP) / (ATP+ADP+AMP) * = The earliest time period when value differed (p< 0.05) from baseline (pre-ischemia). All subsequent values were significantly different from baseline. n ≥ 4 at each time period. (Winn et al., 1979; used with permission)