Search

Introduction: In vitro experiments have demonstrated that preconditioning primary neuronal cultures by temporary application of NMDA receptor antagonists induces long-term tolerance against lethal insults. In the present study we tested whether similar effects also occur in brain submitted to ischemia in vivo and whether the potential benefit outweighs the danger of enhancing the constitutive apoptosis in the developing brain., Material and Methods: Memantine in pharmacologically relevant doses of 5 mg/kg or (+)MK-801 (3 mg/kg) was administered i.p. 24, 48, 72 and 96 h before 3-min global forebrain ischemia in adult Mongolian gerbils or prior to hypoxia/ischemia in 7-day-old rats. Neuronal loss in the hippocampal CA1 in gerbils or weight deficit of the ischemic hemispheres in the rat pups was evaluated after 14 days. Also, the number of apoptotic neurons in the immature rat brain was evaluated., Results: In gerbils only the application of (+)MK-801 24 h before ischemia resulted in significant prevention of the loss of pyramidal neurons. In rat pups administration of (+)MK-801 at all studied times before hypoxia-ischemia, or pretreatment with memantine or with hypoxia taken as a positive control 48 to 92 h before the insult, significantly reduced brain damage. Both NMDA receptor antagonists equally reduced the number of apoptotic neurons after hypoxia-ischemia, while (+)MK-801-evoked potentiation of constitutive apoptosis greatly exceeded the effect of memantine., Conclusions: We ascribe neuroprotection induced in the immature rats by the pretreatment with both NMDA receptor antagonists 48 to 92 h before hypoxia-ischemia to tolerance evoked by preconditioning, while the neuroprotective effect of (+)MK-801 applied 24 h before the insults may be attributed to direct consequences of the inhibition of NMDA receptors. This is the first report demonstrating the phenomenon of inducing tolerance against hypoxia-ischemia in vivo in developing rat brain by preconditioning with NMDA receptor antagonists.

The blood-brain barrier prevents infiltration of peripheral immunocompetent cells into the CNS under physiological conditions. Following brain trauma there is reported a rapid and massive immunological response. Our earlier data indicated that surgical brain injury causes breaking of brain parenchyma integrity and results in cell changes and death, astrogliosis and disruption of blood vessels. The aim of the present studies was to investigate and characterize immunocompetent cells entering brain damaged parenchyma in the early period following the injury in a rat model of surgical damage. In the investigations we used light and electron microscopy techniques. Four days following the lesion many monocytes and macrophages were detected in the injured parenchyma. We also found many activated microglial cells with phagosomes within the cytoplasm. The phagocytes digest the cellular debris and clean up the parenchyma. The data suggest the beneficial role of immunocompetent cells following surgical injury.

Neurosurgical procedures often involve, as a result of the surgeon approaching the diseased region, unavoidable trauma to the adjacent, non-diseased brain structures. Because of the priority of removing the immediate threats to health or life that underlie such interventions, side effects of surgical brain injuries were not given much attention until recently. The cause-and-effect association of the eventual delayed cognitive and/or neurological deficits is often obscure due to substantial potential of the brain for compensatory changes, long life span in man, and aging-related phenomena. However, animal and human studies have demonstrated that physical insults to the brain can initiate a cascade of changes that results, in the long run, in massive neurodegeneration and brain atrophy. Here we present a review of morphological and ultrastructural findings obtained mostly in a rat model of surgical neocortex injury, with consideration of the current view of this region as a network of specific neurovascular units. The neurovascular unit is a dynamic assembly consisting of a capillary vessel, pericytes, neurons and capillary-bound astrocytes. The integrity of this building block and the interactions between its component parts are responsible, among other things, for the proper functioning of the blood-brain barrier, brain blood circulation and the brain as a whole, and its dysregulation is associated with many CNS pathologies. The studies performed in the rat model of surgical brain injury presented in this review have brought new interesting findings regarding the consequences of such damage to the (ultra)structure and hence presumably to the function of the unit. These findings may have some relevance to human clinical situations.

Purinergic ionotropic P2X(7) receptor is widely distributed in brain. Strong evidence suggests that this receptor is related to inflammatory and neurodegenerative changes in many pathological states of central nervous system (CNS), including multiple sclerosis (MS). Experimental autoimmune encephalomyelitis (EAE) is the commonly used animal model of MS. In this study we investigate the expression of P2X(7)R protein in rat brain in the symptomatic phase of EAE (day 10 post immunization) and after reversion of neurological symptoms (day 20 p.i.). We found the increased level of P2X(7)R protein in brain homogenates of EAE rats in both examined time windows. Immunohistochemical study revealed enhanced receptor's immunoreactivity. Immunoblots done with isolated cellular brain fractions indicated that the P2X(7)R overexpression is related to synaptosomal fraction in the symptomatic phase and to the glial (GPV) fraction in the recovery phase of EAE. Concomitantly, we noticed overexpression of astroglial marker GFAP in brain homogenates and astroglial fraction (GPV), so as its enhanced immunoreactivity in brain sections (10 days p.i.) which did not decline to control values in the recovery phase, similarly to P2X(7)R expression. Results suggest the involvement of P2X(7)R-mediated signaling in the pathomechanisms of EAE with the possible relevance of astrocytic pool of cells.