Endothelin-1-induced cerebral ischemia: effects of ketanserin and MK-801 on limb placing in rats.

The long-term effects of the 5-HT(2A) receptor antagonist ketanserin on deficits in sensorimotor integration (limb placing tests) following transient focal cerebral ischemia in rats were compared to the effects of the NMDA antagonist MK-801. Middle cerebral artery occlusion was induced in conscious rats by microinjection of endothelin-1 in the vicinity of the artery (EMCAO model). The EMCAO/vehicle rats exhibited impaired tactile and proprioceptive limb placing. In contrast to ketanserin, MK-801 exerted severe early behavioral disturbances, but both drugs significantly improved the neurological scores much earlier than the spontaneous recovery of function occurred. The present results suggest that pharmacotherapy by means of ketanserin lacking the severe side effects of the NMDA antagonists can be used to enhance functional recovery after stroke.

High-voltage electroencephalogram spindles in rats, aging and 5-HT2 antagonism.

We examined the effects of serotonin-2 (5-hydroxytryptamine-2, 5-HT2) receptor antagonists on the so-called high-voltage spindles (HVS, electroencephalographic patterns, characterized by large amplitude rhythmic waves mainly in the alpha band), recorded from the frontal cortex of young, middle-aged and old freely-moving rats during waking immobility. The study was based on the assumption that the effects of 5-HT2 receptor antagonists on the HVS activity depend on the age of rats, because there is evidence for an age-related decrease in the 5-HT2 binding sites density. Four parameters of the electroencephalogram (EEG) were used to characterize the HVS activity: the square root-transformed EEG peak power in the alpha band, the frequency corresponding to this peak (both measured from the EEG power spectra using the fast Fourier transform), the HVS mean duration, and the HVS incidence (both measured from the EEG records). The EEG parameters were analyzed after i.p. administration of three 5-HT2 receptor antagonists: ketanserin, ritanserin and cyproheptadine. In young rats, the three drugs increased the alpha power, but did not change the alpha peak-corresponding frequency. Ketanserin and ritanserin did not change the HVS mean duration and HVS incidence, while cyproheptadine increased both these parameters in young rats. In middle-aged and old untreated rats, the HVS activity was significantly increased. The three 5-HT2 antagonists did not change the HVS activity in aged rats, which could be due to age-related suppression of the 5-HT2 receptor functions.

Quantitative electroencephalographic changes due to middle cerebral artery occlusion by endothelin 1 in conscious rats.

The powerful vasoconstrictor peptide endothelin-1 (ET1) has been shown to reduce local cerebral blood flow in brain areas supplied by the middle cerebral artery (MCA) to a pathologically low level upon intracerebral injection adjacent to the MCA. This reduction manifests itself as an ischemic infarct, that is fully developed within 3 days after ET1 injection. The aim of the present study is to examine the effect of ET1 on electroencephalographic (EEG) activity. ET1 was microinjected unilaterally at a dose of 60 pmol in 3 microl of saline to the MCA in conscious rats. EEG signals were recorded from the frontoparietal cortical area, supplied by MCA, from the first up to the fourteenth day after ET1 injection. EEG activity was analyzed by the fast Fourier transformation. A significant shift to a lower EEG frequency, i.e., augmentation of slow waves and a reduction of alpha-like and faster EEG waves was found post-ET1. This effect was maximal after 3-7 days when the most severe destruction of neurons in this cortical area occurs, as has been previously demonstrated. The results suggest that the quantitative EEG analysis may provide useful additional information about the functional disturbances associated with focal cerebral ischemia.