Postischemic reperfusion: ultrastructural blood-brain barrier and hemodynamic correlative changes in an awake model of transient forebrain ischemia.
OBJECTIVE
In nonrecovery models of cerebral ischemia, blood-brain barrier (BBB) and cerebral blood flow (CBF) changes are known to occur during reperfusion. It is unknown, however, whether those CBF and BBB alterations occur after brief, transient ischemia with neurological recovery. The purpose of this study was to characterize the time course of CBF and BBB ultrastructural changes during reperfusion in an awake, recovery model of transient global forebrain ischemia (GFI).


METHODS
Forty-five adult Sprague-Dawley rats were subjected, while awake, to 10 minutes of GFI by the nine-vessel occlusion method. Thirty-five age-matched animals composed a sham-operated group. Normal control (n = 5), sham-operated (n = 5), and nine-vessel occlusion/reperfusion (n = 15) rats were selected for ultrastructural analysis. Electroencephalography was performed, and CBF, mean arterial blood pressure, and intracranial pressure were measured during ischemia and reperfusion up to 24 hours. Quantitative morphological analysis of cortical BBB capillaries was performed by transmission electron microscopy at the same time points at which specific CBF changes occurred during reperfusion.


RESULTS
CBF decreased to 6% of preocclusion values during GFI. This correlated with coma and decerebrate rigidity. During reperfusion, short-lived hyperemia (225 +/- 18%, P < 0.001) was characterized by increased intracranial pressure (28.3 +/- 2.6 mm Hg, P < 0.001) and isoelectric electroencephalogram. This was followed by hypoperfusion, which reached a nadir of 59.7% (59.7 +/- 8.8%, P < 0.01) from baseline by 90 minutes. At this time point, the electroencephalogram recovered, and intracranial pressure and mean arterial blood pressure showed no abnormalities. By 8.5 hours, CBF returned to normal, and this coincided with complete recovery of the animal. Ultrastructural BBB analysis revealed astrocyte end-foot process edema and patent capillaries during hyperemia. Severe interstitial BBB edema and capillary lumen collapse was observed during hypoperfusion. Detachment and migration of pericytes was observed during hypoperfusion and beyond.


CONCLUSIONS
A biphasic CBF response is elicited during reperfusion after brief nonlethal GFI under awake conditions.
Melgar
Miguel A
MA
Department of Neurosurgery, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA. mmelgar@tulane.edu
Rafols
Jose
J
Gloss
David
D
Diaz
Fernando G
FG
D000818:Animals; D001253:Astrocytes / Q000648:ultrastructure; D001812:Blood-Brain Barrier / Q000648:ultrastructure*; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D002196:Capillaries / Q000648:ultrastructure; D002560:Cerebrovascular Circulation; D006940:Hyperemia / Q000209:etiology / Q000473:pathology; D019586:Intracranial Hypertension / Q000209:etiology / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D020286:Pericytes / Q000648:ultrastructure; D016548:Prosencephalon / Q000098:blood supply*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D014851:Wakefulness