The microenvironment of the central nervous system (CNS) is precisely and meticulously maintained by a set of dynamic physiological barriers located within the cerebral microvessels of the brain (blood–brain barrier, BBB) and the spinal cord (blood–spinal cord barrier, BSCB), as well as within the epithelial cells of the choroid plexus separating the blood and cerebrospinal fluid (CSF) interface (blood–CSF barrier, BCSFB). The physicochemical properties of these cellular barriers are quite comparable to that of an extended plasma membrane. The BBB and the BSCB are quite tight to small molecules (12 Å, Lanthanum ion), whereas BCSFB is less restrictive in nature. On the other hand, the ependymal cell linings of the cerebral ventricles and spinal canal referred to as CSF–brain barrier do not normally restrict passage of several molecules of small sizes. However, protein transport across these blood–CNS barriers (BCNSB) is severely restricted. Entry of proteins into the CNS microenvironment induces vasogenic edema formation that is primarily responsible for cell and tissue injury. These BCNSB are often compromised under a wide variety of psychological, traumatic, metabolic, ischemic, environmental, or chemical insults leading to neuronal, glial, and axonal damage. Opening of the BCSNB to various endogenous or exogenous substances and proteins alters the molecular, cellular, biochemical, immunological, and metabolic environment of the CNS leading to abnormal neuronal function and/or brain pathology. This review is focused on current status of the BCSNB breakdown in experimental models of emotional stress, traumatic injuries, psychostimulants as well as key environmental health hazards, i.e., nanoparticles and heat exposure. Breakdown of the BCNSB in these conditions altered gene expression and induced brain pathology leading to neurodegeneration. Attenuation of the BCNSB disruption with drugs or antibodies affecting neurochemical metabolism and/or neurotrophic factors markedly reduced the development of brain pathology. Taken together, these novel observations strongly point out the role of BCNSB as a “gateway” to the neurodegeneration, neuroprotection, and/or neuroregeneration in neurological diseases.
Springer, 2009. 363-457 p.