T. Papacocea 1, Raluca Papacocea 2
1 Clinica de Neurochirurgie, Spitalul Clinic de Urgenţă “Sf. Pantelimon” Bucureşti
2 Catedra de Fiziologie I, UMF Carol Davila Bucureşti
Abstract
The blood-brain barrier (BBB) consists of the vascular wall, represented by endothelial cells belonging to cerebral microvessels connected by tight junctions on a basal memebrane and astrocytes which surround the cerebral cappilaries. The astrocytes act as a filter between blood microvessels and neurons, providing the permanent regulation of BBB permeability. A number of pathological instances can injury the BBB, some of these related with the oxidative stress. For instance, the cerebral ischemia is associated with an increase in BBB permeability due to tight junction involvment (Mark et al., 2002). More, free oxigen radicals may increase the transcelular permeability (Cipolla et al., 2004). The oxidative stress increases the proinflamatory cells migration, increases the expression of some cell adhesion molecules and induces the lipidic peroxidation in BBB (Haorah J., 2005). Similary foundings were identified in postmortem samples of brain from patients with Alzheimer disease (AD). More than 30% of patients with AD present cerebrovascular pathology involvind celular elements from BBB structure. AD is the most frequent neurodegenerative progressive disease, characterized by cognitive decline to dementia. Histologically is characterized by senile plaques appeareance, and the main constituent of the plaques is a fibrillar protein, β amiloid (βA). The relation between βA and oxidative stress is still controversial: while some researchers are claiming a prooxidative role (Butterfield DA. et al., 1996) others are showing the opposite: a protective and antioxidant role, acting as an iron/cooper chelator (Cuajungco et al., 2000) or as an antioxidant (Nunomura et al., 2001). In the last decade, the concept of neurovascular unit was introduced and can be applied in AD approaching for a global view of injuries. Together with neuronal injuries, the vascular oxidative aggresion is a target for intense research. It was demonstrated that oxigen and nitrogen free radicals not only decrease the vascular response to various vasodilators, but also can induce a vascular remodeling. The NADPH oxidase was identified as the major source of free radicals because, acting by reducing of vascular NO (nitric oxide) biodisponibility (Park et al. 2005). Cerebral microvessels represent early targets for oxidative stress and βA (Park et al. 2004). The role of the vascular component in AD development is growing and the very early cerebral hypoperfusion could be an important contributant to neuronal and cognitive deficits. (Benarroch, 2007). The BBB increased permeability due to βA deposits in vascular wall, followed by seric protein extravasation (Kumar Sinhg et al, 2005) can also contribute to extravascular damage initiation. The identification of new molecules able to modulate the BBB function in response to oxidative stress aggresion, could be a potential hope for AD patients as much as antioxidants alone were no table to improve the AD evolution (Luchsinger A. J, Tang M.Xet al, 2003).