Histamine Promotes Locomotion Recovery After Spinal Cord Hemisection via Inhibiting Astrocytic Scar Formation

Abstract

Summary: Aim: This study investigated whether histamine could play a protective role in pathophysiological response of spinal cord injury (SCI) and regulate the glial scar formation. Methods: Functional assessment and histological analyses were performed to investigate the effect of histamine after SCI. Histidine decarboxylase knockout (HDC-/-) mice were used to confirm the action of histamine. Selective antagonists for H1 and H2 receptors were utilized in vivo and in vitro to verify the functional properties of histamine on astrogliosis. Results: The local administration of histamine significantly attenuated the tissue damage and glial scar formation after SCI. In particular, the astrogliosis and neurocan expression found around the lesion were significantly suppressed by histamine. Immunofluorescent staining for neurofilament showed that histamine promoted axonal growth across the glial scar. The HDC-/- mice, lacking in endogenous histamine, showed lower behavior score, increased lesion size and astrogliosis, as compared with the wild types. The effect of histamine on locomotor recovery and reactive astrogliosis is reversed by H1 receptor antagonist but not H2 receptor antagonist. Conclusions: Our results indicate that histamine significantly improved the chronic locomotor recovery via attenuating astrogliosis after SCI by stimulating histamine H1 receptor. This study highlights a therapeutic potential of histamine and its related drugs for SCI.