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Journal of Neurosurgical Sciences 2015 Oct 16


lingua: Inglese

Assessment of the neuroprotective effects of the acetylcholinesterase inhibitor Huperzine A in an experimental spinal cord trauma model

Antar V. 1, Baran O. 1, Yuceli S. 2, Erdogan H. 3, Altintas O. 4, Eryigit Baran G. 5, Tasdemiroglu E. 6

1 Istanbul Research and Training Hospital, Neurosurgery Clinic, Istanbul, Turkey; 2 Neon Hospital, Neurosurgery Clinic, Erzincan, Turkey; 3 Maltepe University Medical Faculty, Department of Neurosurgery, Istanbul, Turkey; 4 Nigde Bor State Hospital, Neurology Clinic, Nigde,Turkey; 5 Sisli Hamidiye Etfal Research and Training Hospital, Neurology Clinic, Istanbul, Turkey; 6 Private Consultant, Professor of Neurosurgery, Istanbul, Turkey


BACKGROUND: Spinal cord injury still remains a serious problem and a treatment option, which targets the primary site of injury, does not currently exist. Therefore, the management of acute spinal cord injury has focused on the reasons behind the aggravation of the initial insult through secondary mechanisms, and the search for pharmacological treatment protocols is generally aimed at reducing and minimizing the neural injury and neurological squeal. The secondary spinal cord injury usually develops following a primary lesion induced by spinal cord contusion and the emergence of apoptotic cells has been found to play an important role in the development of secondary injury. We proposed that Huperzine A may induce a significant reduction in the number of apoptotic cells because Huperzine A possesses the ability to protect cells against glutamate, ischemia and staurosporine induced cytotocity and apoptosis. Huperzine A, an alkaloid isolated from the club moss Huperzia serrate, is a potent reversible inhibitor of AChE (acethylcholinesterase) and NMDA receptors.
METHODS: We tested our proposal by administering Huperzine A intraperitoneally to male Wistar Albino rats (220-340 gr body weight) after moderate static clip compression (70 gr for 60 sec) of the spinal cord at T7 level. Neurological functions were assessed using the Basso-Beattle-Breshanan (BBB) motor rating scale until 3th and 7th days before perfusion, following which the spinal cord was harvested for histopathological examinations and apoptotic cell counts.
RESULTS: Histopathological evaluations of the spinal cord of the control, trauma and Huperzine A treated groups were evaluated. Control group showed normal neuronal and vascular structures of the spinal cord. However, in both trauma groups’ 3rd and 7th days’ perfusion showed extensive cavitation and hemorrhage, areas of necrosis and edema in gray matter, and degeneration in motor neurons along with patchy areas of necrotic and apoptotic cells. In Huperzine A treated groups, an increased number of normal cells was noted, and there was a lower number of necrotic cells, with a significant reduction in the apoptotic cells (p < 0.01). The administration of Huperzine A improved posttrauma motor performance. Furthermore, BBB scores of all groups showed that there was an improvement of locomotor abilities in the treatment group as compared with the control.
CONCLUSIONS: When compared with controls, Huperzine A treatment demonstrates a significant reduction in the number of apoptotic cells. In addition, the Huperzine A treated group showed significant and meaningful neurological improvement in rats.

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Antar V, Baran O, Yuceli S, Erdogan H, Altintas O, Eryigit Baran G, et al. Assessment of the neuroprotective effects of the acetylcholinesterase inhibitor Huperzine A in an experimental spinal cord trauma model. J Neurosurg Sci 2015 Oct 16. 

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