Table 1.

Pathophysiology of cerebral ischemia and reperfusion injuries.

Time Course	Pathophysiological Mechanisms
Acute phase (minutes–hours)	Reduced cerebral blood flow with diminished oxygen and glucose delivery Anaerobic metabolism and lactic acidosis Failure of ATPase, cellular depolarization, increased intracellular ion influx Release of neuromediators (excitotoxicity) Increased expression of stress signaling genes
Subacute phase (hours–days)	Increased production of ROS Apoptosis Expression of adhesion molecules Microglial activation and leukocyte infiltration of the brain Release of pro-inflammatory mediators Increased activity of proteolytic enzymes and damage of BBB and endothelium
Chronic phase (days–weeks)	Release of trophic factors (BDNF, IGF, GDNF) Neurogenesis, angiogenesis, synaptogenesis Activation of stem cells

ATPase—adenosine triphosphatase; ROS—reactive oxygen species; BBB—blood–brain barrier; BDNF—brain-derived neurotrophic factor; IGF—insulin-like growth factor; GDNF—glial-derived neurotrophic factor.