Disrupting of blood brain barrier

Related to the post-traumatic microvascular damage is the pathophysiological process of vasogenic brain edema that represents a disruption of blood-brain barrier integrity, resulting in sodium and protein accumulation and osmotic fluid expansion of the brain extracellular space. Clinically, this is reflected by an increase in intracranial pressure which, if unchecked, can cause secondary compressive injury to vital brain structures. 

Clarke, H.B. and Gabrielsen, T.O., Seizure induced disruption of blood-brain barrier demonstrated by CT, J. Comput. Assist. Tomogr, 13(5), 889, 1989. 

Kook SY, Seok Hong H, Moon M, Mook-Jrmg I. Disruption of blood-brain barrier in Alzheimer disease pathogenesis. Tissue Barriers. 2013 l(2) e23993. 

Hypoxia-ischemia disrupts the blood-brain barrier and damages endothelial cells. Damage to the blood-brain barrier (BBB), which occurs gradually following isch-emia-reperfusion, reflects the vulnerability of the cellular... 

Figure 55 Brain images obtained using "mTc-glucoheptonate showing the location of secondary tumors which disrupt the blood brain barrier. (Courtesy of the Nuclear Medicine Department, Queen Elizabeth Hospital, Birmingham, UK)...

Temporal Profile of Blood-Brain Barrier Disruption 141... 

Nervous system In a 67-year-old woman who had had a subarachnoid hemorrhage, intra-arterial papaverine was associated with development of a lesion in the left mesencephalon without a significant mass effect [148" ]. The authors postulated that the papaverine had disrupted the blood-brain barrier, causing extravasation of blood and radiographic contrast agents, possibly facilitated by secondary hyperperfusion. 

Warach S, Latour LL. Evidence of reperfusion injury, exacerbated by thrombolytic therapy, in human focal brain ischemia using a novel imaging marker of early blood-brain barrier disruption. Stroke 2004 35 2659-2661. 

With disruption of this barrier, molecules such as albumin freely enter the brain and ions and water follow. Because the brain lacks a well-developed lymphatic system, clearance of plasma constituents is slow, edema occurs, and intracranial pressure rises. At lower levels of exposure, subtle dysfunction of the blood-brain barrier may contribute to neurobehavioral deficits in children (Bressler and Goldstein 1991 Goldstein 1993). The particular vulnerability of the fetus and infant to the neurotoxicity of lead may be due in part to immaturity of the blood-brain barrier and to the lack of the high-affinity leadbinding protein in astroglia, which is discussed later in this section. Results of measurements of transendothelial electrical resistance across the blood-brain barrier from mice of various ages showed that lead potentiates cytokines-induced increase in ion permeability of the blood-brain barrier (Dyatlov et al. 

C. A. A. M., van der Valk, M. A., RobanusMandaag, E. C., Borst, P., Disruption of the mouse mdrla P-glycoprotein gene leads to a deficiency in the blood brain barrier and to increased sensitivity to drugs, Cell 1994, 77, 491-502. 

Bufotenine has been found to be behaviorally inactive, or only weakly active, in most animal studies, although at 15 mg/kg, it did produce the head-twitch resonse in mice (43). It was also behaviorally active in experiments in which the blood-brain barrier was bypassed (78). Acylation of the polar hydroxy group of bufotenine increases its lipid solubility (65,74) and apparently enhances its ability to cross the blood-brain barrier (64). For example, O-acetylbufotenine (5-acetoxy-N,N-dimethyltryptamine 54) disrupted conditioned avoidance behavior in rodents (65) and produced tremorigenic activity similar to that elicited by DMT (37) or 5-OMeDMT (59) when administered to mice (64). In this latter study, a comparison of brain levels of bufotenine after administration of O-acetylbufotenine with those of DMT and 5-OMeDMT revealed bufotenine to be the most active of the three agents, based on brain concentration. The pivaloyl ester of bufotenine also appears to possess behavioral activity, since stimulus generalization was observed when this agent was administered to animals trained to discriminate 5-OMeDMT from saline (74). 

An important methodologic point about the majority of these studies is that they use a reduced preparation, in which the spinal cord is neurally isolated from the brain by a complete transection (129). The rationale for using this simplified preparation is that spinal reflex activity can be analyzed in the absence of supraspinal influences. However, transection may introduce other variables (i.e., ischemia, disruption of the blood-brain barrier, loss of tonic neural activity from supraspinal systems), which may result in drug effects on spinal reflexes that are quantitatively or even qualitatively different than those seen in the intact animal. Thus the following review of hallucinogen effects on spinal reflexes is organized into two main categories (a) studies in transected animals, and (b) those in decerebrate or intact preparations. 

Uhr M, Grauer MT (2003) abcblab P-glycoprotein is involved in the uptake of citalopram and trimipramine into the brain of mice. J Psychiatr Res 37 179-185 Uhr M, Sleekier T, Yassouridis A, Holsboer F (2000) Penetration of amitriptyhne, but not of fluoxetine, into brain is enhanced in mice with blood-brain barrier deficiency due to mdrla P-glycoprotein gene disruption. Nemopsychopharmacology 22 380-387... 

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