Abstract

During the 17th century, the human body began to be viewed as a system of subunits and independent compartments. This eventually led to the first human anatomical descriptions that mapped the body into different organs and tissues. As a result of this "subunit" or "compartment" theory, the Latin term herniation was employed to describe the protrusion of a portion of an organ or tissue through an abnormal passage. In respect to the central nervous system, brain herniation can result from either supratentorial or subtentorial lesions. Supratentorial masses, such as those that result from lobar hemorrhage, subsequently yield shifts in the brain architecture that can be described as either cingulate, central, or uncal in nature. Cingulate herniation refers to the displacement of the cingulate gyrus under the falx cerebri with subsequent compression of the internal cerebral vein. Downward displacement of the hemisphere with compression of the diencephalon and midbrain through the tentorial notch results in central herniation. Lesions of the frontal, parietal, and occipital lobes can initially precipitate cingulate herniation that progresses to central herniation. The third possibility for brain herniation, known as uncal herniation, involves shift of the temporal lobe, uncus, and hippocampal gyrus toward the midline with compression of the adjacent midbrain. During this process, the ipsilateral third cranial nerve and the posterior cerebral artery are compressed by the uncus and edge of the tentorium. This scenario can result in the well described "blown pupil" that is unilateral, dilated, and fixed, suggesting damage to parasympathetic fibers of the external portion of the third cranial nerve. Obviously, patients with elevated intracranial pressure resulting in cerebral herniation require rapid care to prevent permanent damage to the critical "compartments" of the brains neurovascular unit that consists of neuronal, vascular, and inflammatory cells. The approach is multidisciplinary that begins with a detailed examination of the patient and culminates with several treatment modalities that can involve hyperventilation, fluid restriction, blood pressure control, surgery, and drug therapy that may require osmotic agents, steroids, or barbiturates as indicated. Yet, the availability of true neuroprotective agents to preserve both neuronal and vascular cell integrity is severely limited and successful future development for effective therapies relies directly upon the knowledge of the cellular pathways that impact upon the brains neurovascular unit. In this issue of Current Neurovascular Research, both original and review articles delve into novel cellular pathways that can integrate the function and survival of the neuronal, vascular, and inflammatory components of the neurovascular unit. With our initial article, Taniguchi et al. examine the hypothesis that loss of retinal ganglion cells that can occur during open angle glaucoma may be the result of disturbances in blood flow rather than raised intraocular pressure alone. The authors employ the vasoactive peptide endothelin-1 that is a product of vascular endothelial cells and elegantly demonstrate that intravitreous injection of endothelin-1 in progressive concentrations can lead to the significant constriction of retinal vessels, decrease the retrograde axonal transport in retinal ganglion cells, and lead to histological optic nerve damage. Given that endothelin-1 and its receptors are present in the retina and optic nerve pathways, their work provides fresh evidence for the intricate relationship between neuronal and vascular cells that can impact both normal physiology and disease processes in the nervous system. However, it appears that the neurovascular unit requires the integrity of each of its components, or "sub-compartments", that involve neuronal, vascular, and inflammatory cells to effectively prevent the injury of an organism. For example, Ajmo et al. investigate the neurovascular unit in an experimental model of focal cerebral ischemia. The authors inhibit both sigma-1 and sigma-2 receptor activation following the onset of middle cerebral artery occlusion and show that modulation of sigma receptor activation increases neuronal survival twenty-four hours after the initial insult. These results suggest high clinical relevance for the treatment of patients with stroke.........