In 2000 Clauss & Nel et al were the first to publish a report of an unexpected arousal after zolpidem in a patient catagorized to the Vegetative State after a traumatic brain injury due to a road traffic accident (2). This was followed by other publications including one in 2006 in which three cases were described, two due to motor vehicle accidents. In these patients brain function increased within 30 minutes after oral application of zolpidem years after the accident, with a maximum effect after 1 hour, lasting 2-3 hours (3). Imaging studies using ^99mTc HMPAO Brain SPECT in such patients after brain damage have shown that non-functioning areas start to function again after zolpidem (2, 3). A recent study by Nyakale et al on the efficacy of zolpidem in brain damage included 7 patients after traumatic brain injury (4).  

Zolpidem’s proposed  mode of action is the modulation of ‘abnormal’ GABA receptors that are responsible for Brain dormancy, also called the neurodormant state that occurs after brain injury (3). The neurodormant state is the manifestation of a re-modulated GABA receptor status in areas of the brain. A previous study has shown that certain types of brain suppression are associated with an altered composition of GABA(A) receptor subunits (5). In another study, this suppression was associated with reorganisation of GABA mediation in the cerebellum (6). With normal or borderline GABA levels, GABA receptors remain functioning normally, but in depleted regions such receptors presumably undergo molecular modifications or changes in abundance, possibly due to gene expression, as found in other ischaemic brain conditions (7).

For further information on neurodormancy, please click on the -Brain dormancy theory- in the main menu.

References