Protein transport across cerebral vessels during metrazole-induced convulsions

Abstract

The effects of pentylenetetrazole-induced convulsions on cerebrovascular permeability for horseradish peroxidase were studied in locally anesthetized, artificially respired, paralyzed cats. Horseradish peroxidase circulated for 1, 2.5, 5, 10, 30, and 60 min and accumulated in medium-size, i.e., arterial or venous, blood vessel walls. Cerebral neuropil was permeated earliest in thalamic nuclei including medial and lateral geniculate nuclei. No tight junctions containing horseradish peroxidase were found. With 1.0 and 2.5 min circulation of horseradish peroxidase, arterial adventitia and basement membranes contained more peroxidase than surrounding interstitial space in contrast to veins and capillaries. Convulsions increased the number of endothelial vesicles containing horseradish peroxidase in arteries, veins, and capillaries but total number (stained plus unstained) of endothelial vesicles was increased slightly only in capillaries. We conclude that increased permeability is initially at the arterial level, although veins may also become permeable. The role of the endothelial vesicles in transit or protein in and out of the nervous system is not clear.

Effects of lipopolysaccharide on blood–brain barrier permeability during pentylenetetrazole-induced epileptic seizures in rats

“…On the other hand, the presence of few pinocytotic vesicles in the endothelial cells of cerebral microvessels accounts for a minor transcellular penetration of bloodborne substances (Abbott and Revest, 1991). The two proposed mechanisms by which the BBB opens to macromolecules in epileptic seizure are enhancement of transcellular route by vesicular transport (Westergaard et al, 1978;Petrali et al, 1991) and opening of the tight junctions (Hedley-Whyte et al, 1977). Therefore, determination of the route of macromolecular passage across the BBB could be important in elucidating the pathophysiology of epileptic seizures.…”

Structure and Pathology of the Blood–Brain Barrier

“…In addition, confluent deposits of HRP were observed in abluminal caveolae and the adjacent endothelial basement membranes, which did not otherwise contain tracer ( > Figure 3-4b), suggesting that caveolae were depositing HRP in the endothelial basement membrane and the direction of caveolar passage was from the vascular lumen to the subendothelium. This finding was observed in all subsequent studies of experimental hypertension (Nag et al, 1980;Nag, 1984aNag, , 1986Nag and Harik, 1987) and in other models such as spinal cord injury (Beggs and Waggener, 1976), seizures (Hedley-Whyte et al, 1977), bradykinin-induced BBB breakdown (Raymond et al, 1986), and excitotoxic brain damage (Nag, 1992). The active participation of caveolae in transfer of proteins, such as HRP across cerebral endothelium is supported by the absence of such transport in vessels fixed for 45 min before the perfusion of peroxidase .…”

“…Multifocal areas of HRP extravasation around cerebral vessels were observed in diverse models, such as hypertension (Nag, 1998); spinal cord injury (Beggs and Waggener, 1976); seizures (Hedley-Whyte et al, 1977;Westergaard, 1980;Nitsch et al, 1986); experimental autoimmune encephalomyelitis (Claudio et al, 1989); excitotoxic brain damage (Nag, 1992); brain trauma (Povlishock et al, 1978), brain tumors ; and BBB breakdown induced by bradykinin (Raymond et al, 1986;Hashizume and Black, 2002), histamine (Dux and Joo, 1982), and leukotriene C4 (Hashizume and Black, 2002), and other models as reviewed previously (Nag, 2003b;Lossinsky and Shivers, 2004). In these studies, HRP was present in all layers of the vessel wall and extended into the gap junctions between astrocytic foot processes and into the adjacent extracellular spaces.…”

Effect of dexamethasone on protein extravasation in the brain in acute hypertension induced by amphetamine

“…The main factors thought to be responsible for the BBB to protein are the presence of tight junctions between the endothelial cells and the lack of pinocytotic activity (Reese & Karnovsky 1967). In pressure-induced protein leakage such as in acute hypertension per se and experimental seizures, a number of studies have Hansson et al 1975, Westergaard & Brondstedt 1975, Lorenzo et al 1975, Nag et al 1977, Petito et al 1977, Hedley-White et al 1977, Hansson & Johansson 1978. A marked pinocytotic activity is also seen in amphetamine-induced hypertension (Persson & Johansson, in preparation).…”