title: Assessment of the neuroprotective effects of the acetylcholinesterase inhibitor huperzine A in an experimental spinal cord trauma model.
abstract: BACKGROUND
  Spinal cord injury is nowadays still a challenging disease, and a treatment option aimed at the primary site of injury does not currently exist. Therefore, the management of acute spinal cord injury has recently 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 sequela. 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 propose that huperzine A may induce a significant reduction in the number of apoptotic cells because it possesses the ability to protect cells against glutamate, ischemia and staurosporine-induced cytotocity and apoptosis.
  
  
  METHODS
  Huperzine A was administered intraperitoneally to male Wistar Albino rats (220-340 g of body weight) after moderate static clip compression (70 g for 60 s) 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-day 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 the group treated with huperzine A, an increased number of normal cells was observed, along with a lower number of necrotic cells, with a significant reduction in the apoptotic cells (P<0.01). The administration of huperzine A improved post-trauma 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 group treated with huperzine A showed significant and appreciable neurological improvement in rats.
authors.affiliation: Neurosurgery Clinic, Istanbul Research and Training Hospital, Istanbul, Turkey.
authors.forename: Veysel
authors.initials: V
authors.lastname: Antar
authors.affiliation: Neurosurgery Clinic, Istanbul Research and Training Hospital, Istanbul, Turkey - oguzbaran@gmail.com.
authors.forename: Oguz
authors.initials: O
authors.lastname: Baran
authors.affiliation: Neurosurgery Clinic, Neon Hospital, Erzincan, Turkey.
authors.forename: Sahin
authors.initials: S
authors.lastname: Yuceli
authors.affiliation: Department of Neurosurgery, Medical Faculty, Maltepe University, Istanbul, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Erdogan
authors.affiliation: Neurology Clinic, Nigde Bor State Hospital, Nigde, Turkey.
authors.forename: Ozge
authors.initials: O
authors.lastname: Altintas
authors.affiliation: Neurology Clinic, Sisli Hamidiye Etfal Research and Training Hospital, Istanbul, Turkey.
authors.forename: Gozde E
authors.initials: GE
authors.lastname: Baran
authors.affiliation: Private Consultant, Istanbul, Turkey.
authors.forename: Erol
authors.initials: E
authors.lastname: Tasdemiroglu
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000188:drug therapy*
chemical_list: D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D012717:Sesquiterpenes; C050426:huperzine A