Intraoperative multi-pulse transcranial electric stimulation: the effect of general anesthetics impact on the excitability of the pyramidal tract

The results of intraoperative neurophysiological monitoring during neurosurgical treatment of pathological processes in the central nervous system are analyzed. The mechanisms of action of general anesthetics on the excitability of the pyramidal system during anesthesia with propofol and sevoflurane have been clarified. It has been established that anesthetics with different mechanisms differ in their effect on excitability and conductivity in the system motor neuron of the cortex pathways alpha-motor neuron. Inhalation anesthetic sevoflurane causes a slowdown in the conduction of a nerve impulse and a violation of the mechanisms of convergence of excitation on the alpha-motor neuron of the spinal cord. In this regard, during general anesthesia with sevoflurane, in order to achieve the effectiveness of transcranial electrical stimulation, the number of stimuli in the package should be increased first with a relatively high stimulation current. Under general anesthesia with propofol, the processes of convergence of excitation are not inhibited, therefore, effective electrical stimulation is achieved by increasing the stimulation current with a stable number of stimuli. With an increase in doses of general anesthetic to a level at which periodic patterns are recorded on the electroencephalogram, a deep inhibition of the excitability and conductivity of the pyramidal system occurs. Under these conditions, effective performance of transcranial electrical stimulation is achieved with submaximal values of the current strength and the number of stimuli.

Gamma motor neurons survive and exacerbate alpha motor neuron degeneration in ALS

The molecular and cellular basis of selective motor neuron (MN) vulnerability in amyotrophic lateral sclerosis (ALS) is not known. In genetically distinct mouse models of familial ALS expressing mutant superoxide dismutase-1 (SOD1), TAR DNA-binding protein 43 (TDP-43), and fused in sarcoma (FUS), we demonstrate selective degeneration of alpha MNs (α-MNs) and complete sparing of gamma MNs (γ-MNs), which selectively innervate muscle spindles. Resistant γ-MNs are distinct from vulnerable α-MNs in that they lack synaptic contacts from primary afferent (IA) fibers. Elimination of these synapses protects α-MNs in the SOD1 mutant, implicating this excitatory input in MN degeneration. Moreover, reduced IAactivation by targeted reduction of γ-MNs in SOD1G93Amutants delays symptom onset and prolongs lifespan, demonstrating a pathogenic role of surviving γ-MNs in ALS. This study establishes the resistance of γ-MNs as a general feature of ALS mouse models and demonstrates that synaptic excitation of MNs within a complex circuit is an important determinant of relative vulnerability in ALS.