Neurophysiology and Treatment of Disorders of Consciousness Induced by Traumatic Brain Injury: Orexin Signaling as a Potential Therapeutic Target

: Traumatic brain injury (TBI) can cause disorders of consciousness (DOC) by impairing the neuronal circuits of the ascending reticular activating system (ARAS) structures, including the hypothalamus, which are responsible for the maintenance of the wakefulness and awareness. Current awakening therapies for TBI-induced DOC comprise, among others, the regulation of excitatory and inhibitory neurotransmitters and the stimulation of the peripheral or central nervous system (CNS). However, the effects of these awakening therapies are still not satisfactory. Hypothalamus has been identified as a sleep/wake center, and its anterior and posterior regions have diverse roles in the regulation of the sleep/wake function. In particular, posterior hypothalamus (PH) possesses several types of neurons, including the orexin neurons in the lateral hypothalamus (LH) with widespread projections to other wakefulness-related regions of the brain. Orexins have been known to affect feeding and appetite, and recently their profound effect on sleep disorders and DOC has been identified. Orexin antagonists are used for the treatment of insomnia, and orexin agonists can be used for narcolepsy. Additionally, several studies demonstrated that the agonists of orexin might be effective in the treatment of DOC, providing novel therapeutic opportunities in this field.