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  1. Article ; Online: Novel roles of phentolamine in protecting axon myelination, muscle atrophy, and functional recovery following nerve injury

    Zarin Zainul / Bo Ma / Mert Koka / Jenny L. Wilkerson / Yuma T. Ortiz / Laura Kerosuo / Vijayendran Chandran

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 14

    Abstract: Abstract Incomplete functional recovery after peripheral nerve injury (PNI) often results in devastating physical disabilities in human patients. Despite improved progress in surgical and non-surgical approaches, achieving complete functional recovery ... ...

    Abstract Abstract Incomplete functional recovery after peripheral nerve injury (PNI) often results in devastating physical disabilities in human patients. Despite improved progress in surgical and non-surgical approaches, achieving complete functional recovery following PNI remains a challenge. This study demonstrates that phentolamine may hold a significant promise in treating nerve injuries and denervation induced muscle atrophy following PNI. In a sciatic nerve crush injury mouse model, we found that phentolamine treatment enhanced motor and functional recovery, protected axon myelination, and attenuated injury-induced muscle atrophy in mice at 14 days post-injury (dpi) compared to saline treatment. In the soleus of phentolamine treated animals, we observed the downregulation of phosphorylated signal transducer and activator of transcription factor 3 (p-STAT3) as well as muscle atrophy-related genes Myogenin, muscle ring finger 1 (MuRF-1), and Forkhead box O proteins (FoxO1, FoxO3). Our results show that both nerve and muscle recovery are integral components of phentolamine treatment-induced global functional recovery in mice at 14 dpi. Moreover, phentolamine treatment improved locomotor functional recovery in the mice after spinal cord crush (SCC) injury. The fact that phentolamine is an FDA approved non-selective alpha-adrenergic blocker, clinically prescribed for oral anesthesia reversal, hypertension, and erectile dysfunction makes this drug a promising candidate for repurposing in restoring behavioral recovery following PNI and SCC injuries, axonal neuropathy, and muscle wasting disorders.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Tolerance and dependence to Δ9-tetrahydrocannabinol in rhesus monkeys

    Jenny L Wilkerson / David R Schulze / Lance R McMahon

    PLoS ONE, Vol 14, Iss 3, p e

    Activity assessments.

    2019  Volume 0209947

    Abstract: Cannabis withdrawal upon discontinuation of long-term, heavy Cannabis use is reported in humans; however, methods to establish the nature and intensity of cannabinoid withdrawal, especially directly observable signs, have not been widely established. ... ...

    Abstract Cannabis withdrawal upon discontinuation of long-term, heavy Cannabis use is reported in humans; however, methods to establish the nature and intensity of cannabinoid withdrawal, especially directly observable signs, have not been widely established. This study quantified activity in the home cage of rhesus monkeys and examined the extent to which activity can be used to quantify tolerance to and dependence on Δ9-tetrahydrocannabinol (Δ9-THC). Home-cage activity was measured in one group that received Δ9-THC (1 mg/kg s.c.) every 12 h (i.e., chronic Δ9-THC), and a second group that received Δ9-THC (0.1 mg/kg i.v.) once every 3 days (i.e., intermittent Δ9-THC). Treatment was temporarily discontinued in the chronic Δ9-THC group and the effects of rimonabant and Δ9-THC were examined in both groups. Activity counts were highest during the day (lights on 0600-2000 h) and were lower at night. Rimonabant (0.1-3.2 mg/kg i.v.) dose-dependently increased activity (maximum 20-fold) in the chronic Δ9-THC group but did not significantly alter activity in the intermittent Δ9-THC group. Δ9-THC (0.32-3.2 mg/kg i.v.) dose-dependently decreased activity counts (maximum 4-fold) in both groups but was somewhat more potent in the intermittent as compared with the Δ9-THC group. Discontinuation of Δ9-THC treatment resulted in an immediate (i.e., within 24 h) and time-related increase in activity. The time-related increase in home-cage activity upon abrupt discontinuation of chronic Δ9-THC treatment, as well as the effects of rimonabant to increase activity in monkeys receiving chronic, but not intermittent, Δ9-THC treatment, are consistent with signs of physical dependence on Δ9-THC in primates.
    Keywords Medicine ; R ; Science ; Q
    Subject code 333
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: The Central Role of Glia in Pathological Pain and the Potential of Targeting the Cannabinoid 2 Receptor for Pain Relief

    Jenny L. Wilkerson / Erin D. Milligan

    ISRN Anesthesiology, Vol

    2011  Volume 2011

    Keywords Anesthesiology ; RD78.3-87.3 ; Surgery ; RD1-811 ; Medicine ; R ; DOAJ:Anesthesiology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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