ReviewPharmaceuticals (Basel, Switzerland)2025
Awakening Recovery: Enhancing Orexinergic Tone After Acute CNS Damage.
Review in Pharmaceuticals (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 authors.
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Abstract
Acute injuries to the central nervous system (CNS) share a rapid disruption of arousal, autonomic stability, and neuroimmune balance. Among the neuromodulatory systems affected, the orexin (hypocretin) network is uniquely positioned at the intersection of wakefulness, autonomic control, and motivated behavior. Experimental evidence across ischemic, hemorrhagic, traumatic, and systemic models shows that orexin signaling is sharply suppressed during the early post-injury collapse and gradually recovers as arousal circuits and homeostatic functions stabilize. Controlled enhancement of orexinergic tone has been found to improve arousal state, modulate inflammatory responses, and support behavioral engagement, although these effects are highly dependent on timing, receptor subtype, and physiological context. This review synthesizes evidence from ischemia, hemorrhagic stroke, traumatic brain and spinal cord injury, and systemic inflammatory states, and examines the conceptual and translational rationale for targeting orexin pathways. We summarize available pharmacological, peptide-based, neuromodulatory, and physiological strategies to boost orexinergic tone, highlighting the growing development of selective OX
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