This study explores the neuroprotective action of tumor necrosis factor-a (TNF-a) induced during physical exercise, which, consequently, reduces matrix metalloproteinase-9 (MMP-9) activity and ameliorates blood-brain barrier (BBB) dysfunction in association with extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation. Adult male Sprague-Dawley rats were subjected to exercise on a treadmill for 3 weeks. A 2-h middle cerebral artery occlusion and reperfusion was administered to exercised and nonexercised animals to induce stroke. Exercised ischemic rats were subjected to TNF-a inhibition and ERK1/2 by TNF-a antibody or UO126. Nissl staining of coronal sections revealed the infarct volume. Evans blue extravasation and water content evaluated BBB function. Western blot was performed to analyze protein expression of TNF-a, ERK1/2, phosphorylated ERK1/2, the basal laminar protein collagen IV, and MMP-9. The activity of MMP-9 was determined by gelatin zymography. Tumor necrosis factor-a expression and ERK1/2 phosphorylation were upregulated during exercise. Infarct volume, brain edema, and Evans blue extravasation all significantly decreased in exercised ischemic rats. Collagen IV production increased in exercised rats and remained high after stroke, whereas MMP-9 protein level and activity decreased. These results were negated and returned toward nonexercised values once TNF-a or ERK1/2 was blocked. We concluded that preischemic, exercise-induced TNF-a markedly decreases BBB dysfunction by using the ERK1/2 pathway.

The dual, inhibitory activity of both TNF-alpha and MMP-9 in brain injury suggests that a TNF-alpha and MMP-9 cascade may play a key role in BBB disruption. These results offer a better understanding of the pathophysiology of burn injuries, which may open new avenues for burn treatment beyond the level of current therapies.

No abstract

Fifteen patients evaluated for acute cerebral ischemia underwent acute cerebral revascularization between March, 1979, and May, 1983. Clinical presentation included crescendo transient ischemic attacks (TIA's) in eight cases, progressing neurological dysfunction in three cases, and completed nonfluctuating deficits in four cases. Nine patients received intravenous heparin but did not improve neurologically. The patients with crescendo TIA's were operated on within 4 hours of their last event; those with progressing deficits were operated on while the deficit was developing, and those with established deficits were operated on 4, 6, 9, and 12 hours, respectively, after the event began. The clinical picture for 10 patients had resolved within 10 hours after surgery. One patient with crescendo TIA's, two with progressing deficits, and two with established deficits had postoperative residual deficits, of which three were mild and two severe. One patient, who had a saphenous vein graft to the middle cerebral artery, developed an intracerebral hematoma. In this prospective noncontrolled nonrandomized study, acute cerebral revascularization was performed safely, had limited risks, and offered the potential to help some patients. Further controlled randomized studies are indicated.

A newly modified revascularization procedure for vertebrobasilar insufficiency due to midbasilar stenosis is reported. The approach involves anastomosing the superficial temporal artery to a proximal segment of the superior cerebellar artery. The rationale for the procedure and the surgical technique are discussed.