Alpha2-adrenergic receptor activation reinstates motor deficits in rats recovering from cortical injury

Gabriela García-Díaz; Laura E Ramos-Languren; Carmen Parra-Cid; Joel Lomelí; Sergio Montes; Camilo Ríos; Antonio Bueno-Nava; Ignacio Valencia-Hernández; Rigoberto González-Piña

doi:10.4103/1673-5374.353501

Alpha₂-adrenergic receptor activation reinstates motor deficits in rats recovering from cortical injury

Neural Regen Res. 2023 Apr;18(4):875-880. doi: 10.4103/1673-5374.353501.

Authors

Gabriela García-Díaz¹, Laura E Ramos-Languren², Carmen Parra-Cid³, Joel Lomelí¹, Sergio Montes⁴, Camilo Ríos⁵, Antonio Bueno-Nava³, Ignacio Valencia-Hernández¹, Rigoberto González-Piña⁶

Affiliations

¹ Department of Pharmacology, Section of Postgraduate Studies and Research, High Medical School, Instituto Politécnico Nacional, Salvador Díaz Mirón, Alcaldía Miguel Hidalgo, Mexico City, Mexico.
² Department of Neurobiology of Aging and Brain Damage, Coordination of Psychobiology and Neurosciences, Faculty of Psychology, National Autonomous University of Mexico, Av. Universidad 3040, Col. Copilco Universidad, Alcaldía Coyoacán, Mexico City, Mexico.
³ Direction of Research, National Institute of Rehabilitation LGII, Calz. Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Alcaldía Tlalpan, Mexico City, Mexico.
⁴ Department of Pharmacology, Multidisciplinary Academic Unit Reynosa-Aztlan Reynosa, Autonomous University of Tamaulipas, calle 16 y lago de Chapala, Col. Aztlán, Tamaulipas, Mexico.
⁵ Department of Neurochemistry, National Institute of Neurology and Neurosurgery MVS, Av. Insurgentes Sur 3877, Col. La Fama, Alcaldia Tlalpan, Mexico City, Mexico.
⁶ Department of Pharmacology, Section of Postgraduate Studies and Research, High Medical School, Instituto Politécnico Nacional, Salvador Díaz Mirón, Alcaldía Miguel Hidalgo; Department of Special Education, University of the Americas, Puebla 223, Col. Roma, Alcaldía Cuauhtémoc, Mexico City, Mexico.

Abstract

Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride. Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury. The aim of this study was to analyze the role of α₂-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage. The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours, 3 days, and 20 days after ferrous chloride-induced cortical injury: saline, clonidine, efaroxan (a selective antagonist of α₂-adrenergic receptors) and clonidine + efaroxan. The sensorimotor score, the immunohistochemical staining for α_2A-adrenergic receptors, and norepinephrine levels were evaluated. Eight hours post-injury, the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased, and these effects were maintained 3 days post-injury. However, 20 days later, clonidine administration diminished norepinephrine levels in the pons compared with the sham group. This effect was accompanied by sensorimotor deficits. These effects were blocked by efaroxan. In conclusion, an increase in α₂-adrenergic receptor levels was observed after injury. Clonidine restores motor deficits in rats recovering from cortical injury, an effect that was prevented by efaroxan. The underlying mechanisms involve the stimulation of hypersensitive α₂-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus. The results of this study suggest that α₂ receptor agonists might restore deficits or impede rehabilitation in patients with brain injury, and therefore pharmacological therapies need to be prescribed cautiously to these patients.

Keywords: alpha₂-adrenoceptors; ambulatory behavior; clonidine; cortical injury; efaroxan; functional recovery; immunohistochemistry; motor deficit; norepinephrine; sensorimotor score.