SBNeC 2010
Resumo:J.014


Prêmio
J.014Investigation of the effects of agmatine in a mouse model of traumatic brain injury
Autores:Filipe Carvalho Matheus (UFSC - Universidade Federal de Santa Catarina) ; Tatiana de Luca de Bem (UFSC - Universidade Federal de Santa Catarina) ; Daniel Rial (UFSC - Universidade Federal de Santa Catarina) ; Marcelo Libório Schwarzbold (UFSC - Universidade Federal de Santa Catarina) ; Anicleto Poli (UFSC - Universidade Federal de Santa Catarina) ; Adair Roberto Soares dos Santos (UFSC - Universidade Federal de Santa Catarina) ; Roger Walz (UFSC - Universidade Federal de Santa Catarina) ; Rui Daniel S. Prediger (UFSC - Universidade Federal de Santa Catarina)

Resumo

Objectives: Traumatic brain injury (TBI) has high levels of incidence, mortality and morbidity, causing physical, cognitive and emotional disabilities. Limited specific drug therapy are available for the patients. Evidence has accumulated to suggest that glutamate contribute to hypoxia-ischaemia brain injury. Thus the main objective of this study was to evaluate the effects of the agmatine treatment, which inhibit NMDA subclass of glutamate receptors, in the behavioral impairments induced by TBI in mice. Material and methods: A total of 80 female Swiss adult mice were subjected to a weight-drop model of TBI, using a weight of 12.5 g in free fall of 120 cm. Two hours after TBI induction, the animals received a single intraperitoneal (i.p.) administration of agmatine (10, 30 or 100 mg/kg) or vehicle (NaCl 0,9%). Mice recovered for 10 days and after submitted to a behavioral test battery including: the open field (OF), elevated plus maze (EPM),tail suspension (TS) and the step-down inhibitory avoidance (SD)tests for the evaluation of motor, emotional and cognitive functions, respectively. Results and discussion: In the OF, there were no statistical differences in distance traveled in groups who suffered TBI when compared with control group, showing no impairments in gross locomotor function. In the TS, no changes in the immobility time were observed in groups submitted to TBI when compared with control group. In the EPM the animals who suffered TBI and treated with agmatine at a dose of 100mg/kg exhibited less time (4,7±2,7) and number of entries (0,3±0,1) in open arms when compared to other groups: control (time: 62,8±5,7; entries: 5,4±1,0), TBI (time: 44,0±23,3; entries: 3,1±1,4), TBI+agmatine10 (time: 82,7±19,2; entries: 6,5±1,0) and TBI+agmatine30 (time: 46,4±8,7; entries: 3,7±0,8), thus showing a synergistic anxiogenic effect between TBI and agmatine treatment at this dose. In the SD, animals of the TBI group showed learning and memory deficits when evaluated 1.5 h (median:31,00; 25%percentile:19,75; 75%percentile:44,50) and 24h (median: 32,50; 25%percentile:23,50; 75%percentile: 44,50) when compared with the training session (median: 47,50; 25%percentile:26,75; 75%percentile: 81,00), which was also observed in the group treated with the low tested dose of agmatine (10 mg/kg) (training session - median: 25,00; 25%percentile:13,00; 75%percentile: 47,50; 1,5h - median: 36,00; 25%percentile:18,50; 75%percentile: 59,00; 24h - median: 50,00; 25%percentile:18,00; 75%percentile: 60,00). In groups treated with agmatine at doses of 30 mg/kg (training session - median: 44,00; 25%percentile: 28,50; 75%percentile: 71,25) and 100 mg/kg (training session - median: 37,00; 25%percentile:3,00; 75%percentile: 77,50), there was a reversal of the long-term memory deficits assessed 24h after training (30mg/Kg – median: 125,25; 25%percentile: 53,75; 75%percentile:180,00 and 100mg/Kg – median:180,00; 25%percentile:55,75; 75%percentile: 180,00). Conclusions: Is important to note that agmatine has multiple mechanisms of action interacting with some sites, like NMDA receptors, nitric oxide synthases, alfa-2 receptor and imidazoline receptors which may explain different actions in cognitive and emotional functions. Thereby agmatine may well emerge as a promising complementary therapy for deficits generated by TBI, but requiring adjustments in its use. Financial support: CNPq, CAPES CEUA/UFSC: PP369


Palavras-chave:  TBI, Agmatine, memory