Pentoxifylline treatment improves neurological and neurochemical deficits in rats subjected to transient brain ischemia.
The possible neuroprotector effects of pentoxifylline (P), a methylxanthine derivative and phosphodiesterase inhibitor, were studied on male Wistar rats subjected to a model of transient brain ischemia. One group was treated, 1 h before ischemia (ISC) and 1 h after, with pentoxifylline (P), 50 and 100 mg/kg, i.p. (ISC+P). The other groups were ischemic, ISC; sham operated, SO; P100; SO+P100; and normal controls, N. One week after ischemia, the animals were submitted to the open field, passive avoidance, and water maze tests for evaluating locomotor activity and cognitive deficits, as well as for scintillographic (SPECT) measurements. After these procedures, they were sacrificed and their brain dissected under ice, for histological studies as well as striatal dopamine (DA) and DOPAC measurements by HPLC. In the open field test, ischemia increased locomotor activity, as compared to N, SO, P100 and SO+P100. This parameter was not significantly reversed after P treatment (ISC+P50 or ISC+P100). Grooming behavior was also increased in the ISC group, as compared to all other ones, although only statistically different as compared to the P100 group. The P treatment (ISC+P50 and ISC+P100) brought these values close to normality. In the passive avoidance test, ischemia significantly impaired the short term memory, as compared to the N group, as well as scopolamine (SCP) used as a positive control. In the long term memory, similar effects were observed in the ISC and SCP groups that significantly impaired memory consolidation. P treatment completely reversed the effects observed after ischemia (ISC+P50 and ISC+P100) on the short as well as on the long term memory, and values were similar to those of the P100 group (which increased both parameters, as related to the N group). In the water maze, the ISC group was not different from the N, SO and SO+P100 groups. However, ISC+P50, ISC+P100 and P100 significantly improved the spatial memory, as related to all other groups. SPECT data showed that ischemia produced a lower but significant decrease in brain optical densities, and P brought values close to those seen in the N group. Furthermore, P treatment of the ischemic group (ISC+P50) increased the number of viable hippocampal CA3 neurons, as compared to the ISC group. While ischemia significantly decreased DA levels, the P treatment of ischemic animals brought those values close to normality. In conclusion, P counteracted neurological and neurochemical changes seen after brain ischemia, in rats. The TNF-alpha inhibition and anti-inflammatory actions of P could be responsible, at least in part, for the neuroprotection afforded by the drug.
Bruno
Renata de Barros
Rde B
Department of Biophysiology and Pharmacology, Faculty of Medicine of Juazeiro do Norte-FMJ, Av. Tenente Raimundo Rocha s/n, Juazeiro do Norte, 63040-000, Brazil.
Marques
Tiago Fontenele
TF
Batista
Tiago Melo Teixeira
TM
Lima
Júlio César Sá Silveira
JC
de Arruda
Karla Gleice
KG
Lima
Priscili Fortaleza Souza Fiúza
PF
Santos
Nilton da Silva
Nda S
Cunha
Geanne M A
GM
Vitor
Helio Vitorino Nobre
HV
Viana
Glauce Socorro de Barros
GS
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D006120:Grooming / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010431:Pentoxifylline / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology
D018696:Neuroprotective Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D012601:Scopolamine; D010431:Pentoxifylline; D004298:Dopamine