Impact of neuroinflammation and neurodegeneration on brain homeostasis

Cortical homeostasis is essential for the normal functioning of the brain and to keep the tone of excitability. A tight regulation of ion concentrations, pH, extracellular fluid concentration, perfusion and vascular permeability, turnover of neurotransmitters/mediators and availability of energy supply is necessary to guarantee the neuronal/glial function. In this thesis, the influence of (1) Calcitonin gene-related peptide (CGRP) as a neuroinflammatory neuropeptide that contributes to the pain phase in migraine attacks, (2) Galanin (Gal) as a neuroprotective neuropeptide that can reduce epileptiform neuronal activity, and (3) Alzheimer’s disease (AD) as a neurodegenerative condition on cortical homeostasis has been addressed. The investigated targets were the electrophysiological phenomenon Cortical Spreading Depolarization (CSD) and cortical histopathology. CSD, an en masse depolarization that involved neurons and glial cells, is associated with migraine aura and stroke among other pathologies. The CSD allows the evaluation of cortical homeostasis according to modifications of its parameters (amplitude, propagation velocity, threshold of ignition, numbers of CSD). The expression of neuropeptides and of their receptors in neurons and glial cells was analyzed by immunohistochemistry. The activation of astrocytes and of microglia was confirmed by their morphology and immunohistochemical markers. In the AD-model of TASTPM mice we stained for plaques and activated microglia during ageing and compared them with changes in spontaneous neuronal activity and with parameters of the CSD. First, it was studied ....