Alzheimer’s disease and cerebral ischemia are among the many causative neurodegenerative diseases that lead to disabilities in the middle-aged and elderly population. There are no effective disease-preventing therapies for these pathologies. Recent in vitro and in vivo studies have revealed the TRPC6 channel to be a promising molecular target for the development of neuroprotective agents. TRPC6 channel is a non-selective cation plasma membrane channel that is permeable to Ca²⁺. Its Ca²⁺-dependent pharmacological effect is associated with the stabilization and protection of excitatory synapses. Downregulation as well as upregulation of TRPC6 channel functions have been observed in Alzheimer’s disease and brain ischemia models. Thus, in order to protect neurons from Alzheimer’s disease and cerebral ischemia, proper TRPC6 channels modulators have to be used. TRPC6 channels modulators are an emerging research field. New chemical structures modulating the activity of TRPC6 channels are being currently discovered. The recent publication of the cryo-EM structure of TRPC6 channels should speed up the discovery process even more. This review summarizes the currently available information about potential drug candidates that may be used as basic structures to develop selective, highly potent TRPC6 channel modulators to treat neurodegenerative disorders, such as Alzheimer’s disease and cerebral ischemia.

Spinal cord injury (SCI) is one of the most frequent causes of disability, accompanied by motor and postural impairments, as well as autonomic and behavioural disorders. Since the beginning of the last century, researchers have been developing and refining experimental models of SCI to study pathogenesis and find therapies. Since the beginning of the 20th century, quite a wide range of methods have been developed for contusion and compression injury, complete and partial transection of the spinal cord, and many others. The choice of model subject in such studies was not limited to mammals, but also included amphibians, lampreys, and even fish. Many functional tests have been proposed to assess functional recovery after injury in laboratory animals, ranging from simple rating scales to locomotion kinematics or recording of spinal neuronal activity. This review describes existing models of SCI in most animal species used in neurobiology. Their key characteristics are discussed, which determine the choice of model and model animals depending on the experimental tasks. Each experimental model of SCI has its own advantages and disadvantages determined by species-specific features of spinal cord anatomy and physiology, the speed of recovery from injury, and the ratio of the necrosis zone to the penumbra. The applicability and availability of the proposed methods for assessing the speed and completeness of recovery is also an important factor.

The search for and development of new neuroprotective (or cerebroprotective) drugs, as well as suitable methods for their preclinical efficacy evaluation, are priorities for current biomedical research. Alpha-2 adrenergic agonists, such as mafedine and dexmedetomidine, are a highly appealing group of drugs capable of reducing neurological deficits which result from brain trauma and vascular events in both experimental animals and human patients. Thus, our aim was to assess the effects of mafedine and dexmedetomidine on the brain’s electrical activity in a controlled cortical-impact model of traumatic brain injury (TBI) in rats. The functional status of the animals was assessed by electrocorticography (ECoG), using ECoG electrodes which were chronically implanted in different cortical regions. The administration of intraperitoneal mafedine sodium at 2.5 mg∙kg⁻¹ at 1 h after TBI induction, and daily for the following 6 days, restored interhemispheric connectivity in remote brain regions and intrahemispheric connections within the unaffected hemisphere at post-TBI day 7. Animals that had received mafedine sodium also demonstrated an improvement in cortical responses to photic and somatosensory stimulation. Dexmedetomidine at 25 μg∙kg⁻¹ did not affect the brain’s electrical activity in brain-injured rats. Our results confirm the previously described neuroprotective effects of mafedine sodium and suggest that ECoG registration and analysis are a viable method evaluating drug efficacy in experimental animal models of TBI.

Research and development of novel methods to determine the effects of antipsychotic agents is an important challenge for experimental biomedicine. Although behavioural tests, the ones most commonly used for pharmacological screening, are quite efficient for the evaluation of drug effects on animal anxiety and locomotion, they hardly allow to detect antipsychotic activity. Pharmacoelectroencephalography (pharmaco-EEG), which is based on the principle of different psychoactive agents producing distinct changes in brain electrical activity, could represent a viable alternative approach to that task. The rapid evolution of machine learning techniques has opened new possibilities for using pharmaco-EEG data for the purposes of classification and prediction. This work describes an experimental approach to the assessment of specific activity and pharmacological profiling of antipsychotic agents using naïve Bayes classifier, a simple probabilistic classifier widely employed in biomedical research. The experiments were conducted in white outbred male rats with chronically implanted electrocorticographic electrodes. To serve as the training set, a library was assembled containing electrocorticograms (ECoG) following the administration of antipsychotic agents: chlorpromazine, haloperidol, droperidol, tiapride, and sulpiride. For each sample, ECoG parameters before and after drug administration were calculated, and a total of 132 amplitude and spectral signal parameters were taken into analysis. Principal component analysis was used to reduce dimensionality. Using naïve bayes classifier, we were able to detect and qualify distinct effects of antipsychotic agents on brain electrical activity parameters in rats, allowing them to be differentiated from phenazepam, a benzodiazepine tranquilizer with sedative properties. Moreover, this approach proved effective to distinguish among the antipsychotics as well as between them and other agents with similar receptor binding affinity profiles, e.g., the tricyclic antidepressant amitriptyline. Thus, the method we propose can be used to discern between antipsychotic and sedative effects of drugs as well as to compare the effects across different antipsychotic agents.