Minocycline mitigates motor impairments and cortical neuronal loss induced by focal ischemia in rats chronically exposed to ethanol during adolescence.

Ethanol is an important risk factor for the occurrence of cerebral ischemia contributing to poor prognosis and inefficacy of drug treatments for stroke-related symptoms. Females have a higher lifetime risk for stroke than males. Moreover, female gender has been associated with increased ethanol consumption during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence may potentiate the motor impairments and cortical damage induced by focal ischemia in female rats. We also addressed whether these effects can be mitigated by minocycline, which has been shown to be neuroprotective against different insults in the CNS. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) for 55 days by gavage. Focal ischemia was induced by microinjections of endothelin-1 (ET-1) into the motor cortex. Animals of both groups were treated daily with minocycline (25-50 mg/kg, i.p.) or sterile saline (i.p.) for 5 days, and motor function was assessed using open field, inclined plane and rotarod tests. Chronic ethanol exposure exacerbated locomotor activity and motor coordination impairments induced by focal ischemia in rats. Moreover, histological analysis revealed that microinjections of ET-1 induced pyramidal neuron loss and microglial activation in the motor cortex. Minocycline reversed the observed motor impairments, microglial activation and pyramidal neuron loss in the motor cortex of ischemic rats even in those exposed to ethanol. These results suggest that minocycline induces neuroprotection and functional recovery in ischemic female rats intoxicated with ethanol during adolescence. Furthermore, the mechanism underlying this protective effect may be related to the modulation of neuroinflammation.

Antinociceptive, neurobehavioral and antioxidant effects of Eupatorium triplinerve Vahl on rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Eupatorium triplinerve Vahl belongs to the Asteraceae family, popularly known as Japana. It is a perennial shrub native to Amazon rainforests of South America. Its leaves are used through infusions, decoctions, baths, and tea. It is largely used in Brazilian folk medicine as sedative, febrifuge, stimulant, tonic and anti-inflammatory. AIM OF THE STUDY: The present study evaluated the putative effects of Eupatorium triplinerve on the central nervous system (CNS), including locomotor and anxiety activity, depression-like behavior, and antinociception and oxidative stress. MATERIALS AND METHODS: Two-month-old male Wistar rats (n=7-10 rats/group) and Swiss male and female mice of the species Mus musculus (n=7-10 per group) were administered with 100 mg/kg, 200 mg/kg, 400 mg/kg, 600 mg/kg, and 800 mg/kg of hydroalcoholic extracts of Eupatorium triplinerve (HEET). The behavioral assays included open-field (OF), elevated Plus-maze (EPM), and forced swimming tests (FS). The antinociceptive activity was verified using chemical (acetic acid and formalin) and thermal (hot plate) models of nociception. The oxidative stress levels were measured in rat blood samples after behavioral assays and Trolox equivalent antioxidant capacity (TEAC), nitric oxide and malondialdehyde (MDA) levels were measured in vivo. RESULTS: Oral pretreatment with HEET reduced the locomotion in OF test (200-800 mg/kg), increased central locomotion and open arms entries in the OF and EPM tests, respectively (600-800 mg/kg), and decreased the immobility time in the FS (200-800 mg/kg). It also reduced the writhing number evoked by acetic acid injection (200-800 mg/kg) and licking time in the first phase of the formalin test (400-800 mg/kg). In the oxidative stress assays, the extract decreased TEAC, Nitric Oxide and MDA levels in response to swimming stress induced in rats. CONCLUSIONS: These results were indicative for the first time that Eupatorium triplinerve exerted mild sedative, anxiolytic and antidepressive effects on the CNS. Antinociceptive effects not related to opioid system and antioxidant activity were also observed. These results support the ethnopharmacological use of Eupatorium triplinerve in popular medicine.