title: MLC901, a Traditional Chinese Medicine induces neuroprotective and neuroregenerative benefits after traumatic brain injury in rats.
abstract: Traumatic brain injury (TBI) is a frequent and clinically highly heterogeneous neurological disorder with large socioeconomic consequences. NeuroAid (MLC601 and MLC901), a Traditional Medicine used in China for patients after stroke has been previously reported to induce neuroprotection and neuroplasticity. This study was designed to evaluate the neuroprotective and neuroregenerative effects of MLC901 in a rat model of TBI. TBI was induced by a moderate lateral fluid percussion applied to the right parietal cortex. MLC901 was injected intraperitoneally at 2h post-TBI, and then administered in drinking water at a concentration of 10mg/ml until sacrifice of the animals. The cognitive deficits induced by TBI were followed by using the "what-where-when" task, which allows the measurement of episodic-like memory. MLC901 treatment decreased brain lesions induced by TBI. It prevented the serum increase of S-100 beta (S100B) and neuron-specific enolase (NSE), which may be markers to predict the neurologic outcome in human patients with TBI. MLC901 reduced the infarct volume when injected up to 2h post-TBI, prevented edema formation and assisted its resolution, probably via the regulation of aquaporin 4. These positive MLC901 effects were associated with an upregulation of vascular endothelial growth factor (VEGF) as well as an increase of endogenous hippocampal neurogenesis and gliogenesis around the lesion. Furthermore, MLC901 reduced cognitive deficits induced by TBI. Rats subjected to TBI displayed a suppression of temporal order memory, which was restored by MLC901. This work provides evidence that MLC901 has neuroprotective and neurorestorative actions, which lead to an improvement in the recovery of cognitive functions in a model of traumatic brain injury.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis, 660 Route des Lucioles, 06560 Valbonne, France; Centre Hospitalo-Universitaire de Nice, Hôpital St Roch, 4 rue Pierre Dévoluy, 06000 Nice, France.
authors.forename: H
authors.initials: H
authors.lastname: Quintard
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis, 660 Route des Lucioles, 06560 Valbonne, France.
authors.forename: T
authors.initials: T
authors.lastname: Lorivel
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis, 660 Route des Lucioles, 06560 Valbonne, France.
authors.forename: C
authors.initials: C
authors.lastname: Gandin
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis, 660 Route des Lucioles, 06560 Valbonne, France.
authors.forename: M
authors.initials: M
authors.lastname: Lazdunski
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis, 660 Route des Lucioles, 06560 Valbonne, France. Electronic address: heurteau@ipmc.cnrs.fr.
authors.forename: C
authors.initials: C
authors.lastname: Heurteaux
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D008297:Male; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; C546417:Neuroaid; D018696:Neuroprotective Agents; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D010751:Phosphopyruvate Hydratase
keywords: NeuroAid; VEGF; aquaporins; cognitive deficits; neurogenesis; traumatic brain injury