In pathology and anatomy the penumbra is the area surrounding an ischemic event such as an ischemic, thrombotic or embolic stroke. Immediately following the event, blood flow and therefore oxygen transport is reduced locally, leading to hypoxia of the cells near the location of the original insult. This can lead to hypoxic cell death (infarction) and amplify the original damage from the ischemia; however, the penumbra area may remain viable for several hours after an ischemic event due to the collateral arteries that supply the penumbral zone.
As time elapses after the onset of stroke, the extent of the penumbra tends to decrease; therefore, in the emergency department a major concern is to protect the penumbra by increasing oxygen transport and delivery to cells in the danger zone, thereby limiting cell death. The existence of a penumbra implies that salvage of the cells is possible. There is a high correlation between the extent of spontaneous neurological recovery and the volume of penumbra that escapes infarction; therefore, saving the penumbra should improve the clinical outcome.
One widely accepted definition for penumbra describes the area as "ischemic tissue potentially destined for infarction but not yet irreversibly injured and the target of acute therapies."  The original definition of the penumbra referred to areas of the brain that were damaged but not yet dead, and offered promise to rescue the brain tissue with the appropriate therapies.
The penumbra region typically occurs when blood flow drops below 20 mL/100 g/min. At this point electrical communication between neurons fails to exist.Cells in this region are alive but metabolic pumps are inhibited, oxidative metabolism is reduced but neurons may begin to depolarize again. Areas of the brain generally do not become infarcted until blood flow to the region drops below 10 to 12 mL/100 g/min. At this point, glutamate release becomes unregulated, ion pumps are inhibited and adenosine triphosphate (ATP) synthesis also stops which ultimately leads to the disruption of intracellular processes and neuronal death.
Identification by imaging
PET is the gold standard for imaging, but because PET is neither widely available nor rapidly accessible current research focuses on improved MRI techniques. The penumbral area can also be detected based upon an integration of three factors. These factors include: the site of vessel occlusion, the extent of oligaemia (hypoperfused area surrounding the penumbra, but not at risk of infarction ) at that moment, and the mismatch between this perfusion defect and the area of the brain already infarcted 
The penumbral areas have significant functional implications in terms of patients' regaining their motor ability. In order to save these penumbral areas as best as possible, health care professionals will often administer a blood thinner to dissolve the blockages in the affected area that are causing the lack of blood flow. Best efforts should be made to saving penumbral areas, as research has demonstrated that the amount of penumbral tissue saved and spontaneous neurologic recovery are closely related.
The first decade of research focused on physiologic profile of the penumbra tissue after stroke, mapping the cerebral blood flow, and quantifying oxygen and glucose consumption to define these areas. The second decade revealed the mechanism of the neuronal cell death. As the Biochemical pathways were dissected penumbral science became a rapidly evolving area of molecular biology. The third decade of penumbral research found a transitional leap as using Positron Emission Tomography (PET) scanning can identify brain tissue with decreased blood flow and Magnetic Resonance Imaging (MRI) has the ability to detect portions of the ischemic tissue that has not yet died. These images have allowed vision into the brain to see the areas of tissue that may be salvaged, the penumbra. Research has now entered into the fourth decade, which leaves researchers wondering why the penumbra has failed as there has not been a neuroprotectant found. A deeper dissection of the penumbra may be needed to make the huge leap to viable clinical therapies as research still tries to understand the complex response of stroke and the transitional zones between injury and repair.
- Guadagno J., Calautti C., Baron J. (2003). "Progress in imaging stroke: emerging clinical applications". British Medical Bulletin 65 (1): 145–157. doi:10.1093/bmb/65.1.145.
- Fisher M, Ginsberg M (2004). "Current Concepts of the Ischemic Penumbra". Stroke 32: 2657. doi:10.1161/01.STR.0000143217.53892.18.
- Eng H Lo. (2008). "A New Penumbra: Transitioning from injury into repair after stroke". Nature Medicine 14 (5): 497–500. doi:10.1038/nm1735.
- Hakim (September 1998). "The penumbra: The therapeutic window". Neurology 31 (3): 44–6. doi:10.1212/wnl.51.3_suppl_3.s44. PMID 9744833.
- Rowley, H. (2001) The four p's of acute stroke imaging: parenchyma, pipes, perfusion, and penumbra. American Journal of Neuroradiology 22: 599-601.
- Herholz, K. (2000). "Functional Imaging Correlates of Recovery After Stroke in Humans". Journal of Cerebral Blood Flow and Medicine 20: 619–631.