TY - JOUR
T1 - Alpha 2 -adrenergic receptor activation reinstates motor deficits in rats recovering from cortical injury
AU - García-Díaz, Gabriela
AU - Ramos-Languren, Laura E.
AU - Parra-Cid, Carmen
AU - Lomelí, Joel
AU - Montes, Sergio
AU - Ríos, Camilo
AU - Bueno-Nava, Antonio
AU - Valencia-Hernández, Ignacio
AU - González-Piña, Rigoberto
N1 - Publisher Copyright:
© 2023 Wolters Kluwer Medknow Publications. All rights reserved.
PY - 2023/4
Y1 - 2023/4
N2 - 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 α 2 -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 α 2 -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 α 2 -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 α 2 -adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus. The results of this study suggest that α 2 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.
AB - 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 α 2 -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 α 2 -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 α 2 -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 α 2 -adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus. The results of this study suggest that α 2 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.
KW - alpha2-adrenoceptors
KW - ambulatory behavior
KW - clonidine
KW - cortical injury
KW - efaroxan
KW - functional recovery
KW - immunohistochemistry
KW - motor deficit
KW - norepinephrine
KW - sensorimotor score
UR - http://www.scopus.com/inward/record.url?scp=85139759849&partnerID=8YFLogxK
U2 - 10.4103/1673-5374.353501
DO - 10.4103/1673-5374.353501
M3 - Artículo
C2 - 36204857
AN - SCOPUS:85139759849
SN - 1673-5374
VL - 18
SP - 875
EP - 880
JO - Neural Regeneration Research
JF - Neural Regeneration Research
IS - 4
ER -