TY  - JOUR
PY  - 2023//
TI  - Recovery from traumatic brain injury (TBI) is Nociceptin/Orphanin FQ peptide (NOP) receptor genotype-, sex-, and injury severity-dependent
JO  - Journal of pharmacology and experimental therapeutics
A1  - Al Yacoub, Omar N.
A1  - Awwad, Hibah O.
A1  - Standifer, Kelly M.
SP  - ePub
EP  - ePub
VL  - ePub
IS  - ePub
N2  - Traumatic brain injury (TBI) is a leading cause of death and disability in the United States and survivors often experience mental and physical health consequences that reduce quality of life. We previously reported that blockade of the nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor reduced tissue damage markers produced by blast TBI. The goal of this study was to determine the extent to which N/OFQ and NOP receptor levels change following mild (mTBI) and moderate TBI (modTBI) and whether the absence of the NOP receptor attenuates TBI-induced sequelae. Male and female NOP receptor knockout (KO) or wild-type (WT) rats received craniotomy-only (sham), or craniotomy plus mild (mTBI), or moderate TBI (modTBI) impact to the left cerebral hemisphere. Neurological and vestibulomotor deficits, and nociceptive hyperalgesia and allodynia found in WT male and female rats following mTBI and modTBI were greatly reduced or absent in NOP receptor KO rats. NOP receptor levels increased in brain tissue from injured males but remained unchanged in females. NF-L and GFAP expression were reduced in NOP receptor KO rats compared to WT following TBI. Levels of N/OFQ in injured brain tissue correlated with neurobehavioral outcomes and GFAP in WT males, but not with KO male or WT and KO female rats. This study reveals a significant contribution of the N/OFQ-NOP receptor system to TBI-induced deficits and suggests that the NOP receptor should be regarded as a potential therapeutic target for TBI. Significance Statement This study revealed that NOP receptor KO animals experienced fewer TBI-induced deficits than their WT counterparts in a sex- and injury severity-dependent manner, suggesting that NOP receptor antagonists may be a potential therapy for TBI.<p />  <p>Language: en</p>
LA  - en
SN  - 0022-3565
UR  - http://dx.doi.org/10.1124/jpet.123.001664
ID  - ref1
ER  -