Evolutionary concept of inflammatory response and stroke.

The immune system plays an important role under both physiological and pathological conditions. Immune surveillance as well as defense and healing processes are crucial for the organism, but the immune system has a natural tendency to act aggressively when excessively stimulated. We may assume that the immune system is not designed to deal with severe conditions, such as polytrauma or severe stroke, because these are not compatible with life in the wilderness and evolution has no chance to act in such cases. These conditions are associated with exaggerated/deregulated inflammatory response, which may cause more damage than initial pathology. In this article, we would like to sketch a basic concept of the immune system-brain interactions from the evolutionary point of view and to discuss some implications related to stroke.

Early Inflammatory Response in the Brain and Anesthesia Recovery Time Evaluation After Experimental Subarachnoid Hemorrhage.

The main objective was to evaluate, whether the subarachnoid hemorrhage (SAH)-associated early inflammatory response has focal or global character, i.e., whether areas distant to hematoma may be affected by an early inflammatory response. The second objective was to evaluate the association of anesthesia recovery time for basic reflexes/neurological functions with severity of SAH. SAH was induced in rats using an endovascular perforation model. Anesthesia recovery time was evaluated for pain reaction recovery time (spinal level), spontaneous ventilation recovery time (brain stem level), and consciousness recovery time (neocortical level). mRNA expressions of TNFα, IL-1ß, IL-6, ICAM-1, and VCAM-1 in areas adjacent and distant to hematoma were evaluated between 2 and 8 h after SAH. Serum levels of TNFα, IL-1ß, and IL-6 were assessed at 4 and 8 h after SAH. Anesthesia recovery time of all selected parameters was associated with severity of SAH. The consciousness recovery time test had the best predictive value, while the spontaneous ventilation recovery time test was able to bring information in the shortest time. The mRNA expressions of pro-inflammatory cytokines were significantly increased in severe SAH groups in both adjacent and distant areas. The inflammatory response in mild/moderate SAH groups was less strong, peaking at 4 h after SAH. Serum levels of pro-inflammatory cytokines were ambiguous. Anesthesia recovery time may be useful for bleeding severity prediction in the SAH model; however, further validation is needed. Severe subarachnoid hemorrhage is associated with the strong early inflammatory response, which has a global character, while mild subarachnoid hemorrhage is accompanied by a weaker inflammation.

The Role of Inflammatory Response in Stroke Associated Programmed Cell Death.

Stroke represents devastating pathology which is associated with a high morbidity and mortality. Initial damage caused directly by the onset of stroke, primary injury, may be eclipsed by secondary injury which may have a much more devastating effect on the brain. Primary injury is predominantly associated with necrotic cell death due to fatal insufficiency of oxygen and glucose. Secondary injury may on the contrary, lead apoptotic cell death due to structural damage which is not compatible with cellular functions or which may even represent the danger of malign transformation. The immune system is responsible for surveillance, defense and healing processes and the immune system plays a major role in triggering programmed cell death. Severe pathologies, such as stroke, are often associated with deregulation of the immune system, resulting in aggravation of secondary brain injury. The goal of this article is to overview the current knowledge about the role of immune system in the pathophysiology of stroke with respect to programmed neuronal cell death as well as to discuss current therapeutic strategies targeting inflammation after stroke.