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Spinal cord injury (SCI) can bring about a modification that weakens the inhibitory effect of GABA in the central gray caudal to injury. This change is linked to the downregulation of the potassium\/chloride cotransporter (KCC2) and the consequent rise in intracellular Cl\u2212 in the postsynaptic neuron. As the intracellular concentration increases, the inward flow of Cl\u2212 through an ionotropic GABA-A receptor is reduced, which decreases its hyperpolarizing (inhibitory) effect, a modulatory effect known as ionic plasticity. The loss of GABA-dependent inhibition enables a state of over-excitation within the spinal cord that fosters aberrant motor activity (spasticity) and chronic pain. A downregulation of KCC2 also contributes to the development of a number of brain-dependent pathologies linked to states of neural over-excitation, including epilepsy, addiction, and developmental disorders, along with other diseases such as hypertension, asthma, and irritable bowel syndrome. Pharmacological treatments that target ionic plasticity have been shown to bring therapeutic benefits.<\/jats:p>","DOI":"10.3390\/cells11182910","type":"journal-article","created":{"date-parts":[[2022,9,18]],"date-time":"2022-09-18T22:12:43Z","timestamp":1663539163000},"page":"2910","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Ionic Plasticity: Common Mechanistic Underpinnings of Pathology in Spinal Cord Injury and the Brain"],"prefix":"10.3390","volume":"11","author":[{"given":"Kelsey E.","family":"Hudson","sequence":"first","affiliation":[{"name":"Neuroscience, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Grau","sequence":"additional","affiliation":[{"name":"Psychological & Brain Sciences, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,17]]},"reference":[{"key":"ref_1","unstructured":"Golan, D.E. 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