[1]. At the center of an infarct, blood flow is completely absent, causing neurons to die within a matter of minutes. This area, therefore, may not be amenable to treatment after the start of symptoms. The region of the brain that draws the most interest is the penumbra,

where evidence has shown that blood flow is diminished, but not absent. The cells in this region remain viable for a prolonged period, and can Selleck Alpelisib be saved if adequate perfusion is restored [2]. The only FDA approved therapies for acute ischemic stroke include tPA, and interventional intra-arterial treatments aimed at restoring blood flow to the ischemic penumbra [3], [4], [5] and [6], but must be used within the first few hours of the onset of symptoms [7] and [8].

There is also evidence that a percentage of the cells subjected to prolonged ischemia will inevitably undergo apoptosis, either after prolonged ischemia or due to reperfusion injury in the case of temporary ischemia [9], [10], [11] and [12]. As a result, there has been great interest in using HBO2T for the added benefit of its anti-inflammatory and anti-apoptotic properties Epacadostat supplier [13], [14], [15], [16], [17] and [18]. There is reasonable evidence from animal studies, involving mice, rats, gerbils, and cats that damage from focal cerebral ischemia is ameliorated after treatment with HBO2T (1). Several human trials investigating the use of HBO2T for ischemic

stroke have also been performed. Most of these lacked controls, as well as uniform standards for inclusion criteria and outcome measurement. There have been three prominent randomized Casein kinase 1 controlled studies that have evaluated HBO2T in ischemic stroke, none of which where able to demonstrate statistically significant benefit [19], [20] and [21]. One might conclude from this that HBO2T is an ineffective treatment for ischemic stroke, however, it should be noted that these studies enrolled patients well after the therapeutic window of 6–12 h suggested by previous animal studies. Additionally, two of the three also used lower doses of HBO2T than was found effective in animal studies. Based on our present understanding of ischemia, one would not expect improvement in measured outcomes under these conditions. It seems therefore reasonable to assess patients presenting for potential HBO2T for a pattern of penumbra as this provides the strongest evidence of recoverable tissue. As the ischemic penumbra represents the area which is expected to be most salvageable, it is reasonable to determine whether a penumbra is or is not present in patients undergoing experimental treatment with HBO2T On MRI, penumbra is represented by perfusion–diffusion mismatch [6]. More simply stated, we must find the area of brain which is dying in hope that HBO2T can still save it before it is dead. This is called ischemic penumbra.