title: Treatment with Actovegin improves spatial learning and memory in rats following transient forebrain ischaemia.
abstract: This study aimed to investigate whether Actovegin, which is a deproteinized ultrafiltrate derived from calf blood, demonstrates neuroprotective effects in a rat model of transient global cerebral ischaemia. Forty Sprague Dawley rats were subjected to four-vessel occlusion to induce transient global cerebral ischaemia followed by either saline or Actovegin treatment. Sham operations were performed on 15 rats. Actovegin (200 mg/kg) or saline was administered 6 hrs after carotid artery occlusion and then daily until Day 40. Learning and memory were evaluated using the Morris water maze test over two different 5-day periods, and grip strength testing was also performed to control for potential motor impairments. Rat brains were harvested for histological analysis on Day 68. In comparison to controls, Actovegin-treated rats exhibited a decreased latency to reach the hidden platform on the second learning trial of water maze testing (46.82 ± 6.18 versus 27.64 ± 4.53 sec., P < 0.05; 38.3 ± 8.23 versus 13.37 ± 2.73 sec., P < 0.01 for the first and second 5-day testing periods, respectively). In addition, Actovegin-treated rats spent more time in the platform quadrant than saline-treated rats during memory trials (P < 0.05). No differences in grip strength were detected. Histological analyses demonstrated increased cell survival in the CA1 region of the hippocampus following Actovegin treatment (left hemisphere, 166 ± 50 versus 332 ± 27 cells, P < 0.05; right hemisphere, 170 ± 45 versus 307 ± 28 cells, P < 0.05, in saline- versus Actovegin-treated rats, respectively). In rats, Actovegin treatment improves spatial learning and memory following cerebral ischaemia, which may be related to hippocampal CA1 neuroprotection.
authors.affiliation: Neurology Service, MD Biosciences Ltd, Nes-Ziona, Israel.
authors.forename: Sigal
authors.initials: S
authors.lastname: Meilin
authors.forename: Fausto
authors.initials: F
authors.lastname: Machicao
authors.forename: Martin
authors.initials: M
authors.lastname: Elmlinger
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D006418:Heme / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D065853:Spatial Learning / Q000187:drug effects / Q000502:physiology*
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D006418:Heme; C015646:Actovegin
keywords: actovegin; ischaemia; learning; memory; neuroprotection; stroke