Ionic Plasticity: Common Mechanistic Underpinnings of Pathology in Spinal Cord Injury and the Brain
The neurotransmitter GABA is normally characterized as having an inhibitory effect on neural activity in the adult central nervous system (CNS), which quells over-excitation and limits neural plasticity. Spinal cord injury (SCI) can bring about a modification that weakens the inhibitory effect of GA...
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MDPI AG
2022-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/18/2910 |
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| author | Kelsey E. Hudson James W. Grau |
| author_facet | Kelsey E. Hudson James W. Grau |
| author_sort | Kelsey E. Hudson |
| collection | DOAJ |
| description | The neurotransmitter GABA is normally characterized as having an inhibitory effect on neural activity in the adult central nervous system (CNS), which quells over-excitation and limits neural plasticity. 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<sup>−</sup> in the postsynaptic neuron. As the intracellular concentration increases, the inward flow of Cl<sup>−</sup> 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. |
| first_indexed | 2024-03-10T00:25:31Z |
| format | Article |
| id | doaj.art-344138791f4a43bc88e82b66f31395be |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:25:31Z |
| publishDate | 2022-09-01 |
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| spelling | doaj.art-344138791f4a43bc88e82b66f31395be2023-11-23T15:34:16ZengMDPI AGCells2073-44092022-09-011118291010.3390/cells11182910Ionic Plasticity: Common Mechanistic Underpinnings of Pathology in Spinal Cord Injury and the BrainKelsey E. Hudson0James W. Grau1Neuroscience, Texas A&M University, College Station, TX 77843, USAPsychological & Brain Sciences, Texas A&M University, College Station, TX 77843, USAThe neurotransmitter GABA is normally characterized as having an inhibitory effect on neural activity in the adult central nervous system (CNS), which quells over-excitation and limits neural plasticity. 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<sup>−</sup> in the postsynaptic neuron. As the intracellular concentration increases, the inward flow of Cl<sup>−</sup> 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.https://www.mdpi.com/2073-4409/11/18/2910spinal cord injuryGABAionic plasticitypainspasticityepilepsy |
| spellingShingle | Kelsey E. Hudson James W. Grau Ionic Plasticity: Common Mechanistic Underpinnings of Pathology in Spinal Cord Injury and the Brain Cells spinal cord injury GABA ionic plasticity pain spasticity epilepsy |
| title | Ionic Plasticity: Common Mechanistic Underpinnings of Pathology in Spinal Cord Injury and the Brain |
| title_full | Ionic Plasticity: Common Mechanistic Underpinnings of Pathology in Spinal Cord Injury and the Brain |
| title_fullStr | Ionic Plasticity: Common Mechanistic Underpinnings of Pathology in Spinal Cord Injury and the Brain |
| title_full_unstemmed | Ionic Plasticity: Common Mechanistic Underpinnings of Pathology in Spinal Cord Injury and the Brain |
| title_short | Ionic Plasticity: Common Mechanistic Underpinnings of Pathology in Spinal Cord Injury and the Brain |
| title_sort | ionic plasticity common mechanistic underpinnings of pathology in spinal cord injury and the brain |
| topic | spinal cord injury GABA ionic plasticity pain spasticity epilepsy |
| url | https://www.mdpi.com/2073-4409/11/18/2910 |
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