RESUMEN
There is evidence that the blood-brain barrier (BBB) is breached following traumatic brain injury (TBI), allowing the unregulated entry of circulating neuroactive substances into the central nervous system. As the traumatic episode is typically associated with an acute hypertensive event, which in itself may alter BBB status, the effects of the blockade of TBI-associated hypertension on injury-associated behavioral and cerebrospinal fluid (CSF) neurochemical changes were assessed in rats. Animals were injected with either saline or hexamethonium 15 min prior to a moderate fluid percussion injury while under light methoxyflurane anesthesia. This dose of hexamethonium was demonstrated to block the hypertensive response to TBI. Pretreatment with hexamethonium prevented neither acute nor more enduring behavioral deficits observed after TBI. Hexamethonium did not prevent TBI-associated increases in CSF acetylcholine (ACh) content in separate group of rats sampled 12 min following TBI. Furthermore, histological inspection indicated that hexamethonium did not prevent TBI-induced disruption of the BBB, as assessed by intravascular horseradish peroxidase (HRP). Thus, blockade of the hypertensive response to TBI does not afford behavioral protection nor does it prevent changes in the BBB or CSF ACh content following TBI. TBI is in itself sufficient to modify behavior, neurochemistry and BBB function in the absence of hypertension.
Asunto(s)
Acetilcolina/líquido cefalorraquídeo , Conducta Animal/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Lesiones Encefálicas/fisiopatología , Compuestos de Hexametonio/farmacología , Hipertensión/fisiopatología , Análisis de Varianza , Animales , Transporte Axonal , Encéfalo/patología , Lesiones Encefálicas/líquido cefalorraquídeo , Reacción de Fuga/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Hexametonio , Peroxidasa de Rábano Silvestre , Hipertensión/prevención & control , Masculino , Actividad Motora/efectos de los fármacos , Postura , Ratas , Ratas EndogámicasRESUMEN
The effect of prenatal exposure to methadone via maternal osmotic minipumps was studied on brain regional acetylcholine (ACh) turnover and dopamine (DA), norepinephrine (NE), serotonin (5-hydroxytryptamine, 5-HT) and their metabolites in 21-day-old female and male rats. ACh content was not affected in any region studied. However, the turnover rate of ACh (TRAch) was increased significantly in the striata and parietal cortices of both sexes. Two gender-specific changes were observed: a profound decrease in hypothalamic TRACh in the females and an increase in hippocampal TRACh in the males. No changes were observed in TRACh in the medulla-pons or the frontal cortex of either sex. The reduction in TRACh was accompanied by a threefold increase in DA content in the hypothalamus of the methadone-exposed females. No other changes were observed in DA, NE, or 5-HT, save for increased 5-HT content in the medulla-pons of the male methadone-exposed rats. Thus, prenatal methadone exposure produces several lingering changes in cholinergic function, many of which were not apparent in the immediate postnatal period. Although striatal ACh content was no longer reduced in methadone-exposed rats, striatal cholinergic function remains disrupted. It remains to be proven whether these differences are a direct effect of methadone exposure or are a consequence of neonatal withdrawal.