Opioid Receptor Antagonists Attenuate Heat Stress‐Induced Reduction in Cerebral Blood Flow, Increased Blood‐Brain Barrier Permeability, Vasogenic Edema and Cell Changes in the Rat<sup>a</sup>

Sharma, Hari Shanker; Westman, Jan; Cervós-Navarro, J.; Dey, Prasanta Kumar; Nyberg, Fred

doi:10.1111/j.1749-6632.1997.tb51747.x

Cited by 48 publications

(16 citation statements)

References 30 publications

(82 reference statements)

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“…Most of the effects of dynorphin, the natural ligand of κ-opioid receptor could be blocked by high doses of naloxone [332]. Alternatively, naloxone in high doses reduces trauma induced "neuronal shock" and alleviates cellular stress response [336]. A decrease in neuronal shock and/or cellular stress response in SCI improves SCEP activity.…”

Section: High Doses Of Naloxone Is Neuroprotectivementioning

confidence: 98%

Pathophysiology of Blood-Spinal Cord Barrier in Traumatic Injury and Repair

Sharma¹

2005

CPD

157

218

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Blood-spinal cord barrier (BSCB) plays an important role in the regulation of the fluid microenvironment of the spinal cord. Trauma to the spinal cord impairs the BSCB permeability to proteins leading to vasogenic edema formation. Several endogenous neurochemical mediators and growth factors contribute to trauma induced BSCB disruption. Studies carried out in our laboratory suggest that those drugs and neurotrophic factors capable to attenuate the BSCB dysfunction following trauma are neuroprotective in nature. Whereas, agents that do not exert any influence on the BSCB disruption failed to reduce cell injury. These observations are in line with the idea that BSCB disruption plays an important role in the pathophysiology of spinal cord injuries. The probable mechanism(s) of trauma induced BSCB dysfunction and its contribution to cell injuries are discussed.

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Section: High Doses Of Naloxone Is Neuroprotectivementioning

confidence: 98%

Pathophysiology of Blood-Spinal Cord Barrier in Traumatic Injury and Repair

Sharma¹

2005

CPD

157

218

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“…In separate group of rats fresh spinal cord tissues from the T9 and T12 segments were used for determination of spinal cord water content and microvascular permeability to [~31]I-sodium (Sharma et al, 1997b). For this purpose radioactive iodine (about 0.5 x 106 cpm) in 0.9% saline was injected into the right femoral vein 5 rain before termination of the experiment.…”

Section: Nos Irnmunohistochemistrymentioning

confidence: 99%

“…Tissue pieces from T9, T10-11 and T12 were dissected out, weighed immediately and counted in a 3-in well type gamma counter (energy window 500-800 KeV). After counting the radioactivity the tissue samples were dried in an incubator maintained at 90°C for 72 h (Sharma et al, 1997b).…”

Section: Nos Irnmunohistochemistrymentioning

confidence: 99%

Brain derived neurotrophic factor and insulin like growth factor-1 attenuate upregulation of nitric oxide synthase and cell injury following trauma to the spinal cord

Sharma

Nyberg²,

Westman

et al. 1998

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The possibility that brain derived neurotrophic factor (BDNF) and insulin like growth factor-1 (IGF) induced neuroprotection is influenced by mechanisms involving nitric oxide was examined in a rat model of focal spinal cord injury. BDNF or IGF-I (0.1 microgram/10 microliters in phosphate buffer saline) was applied topically 30 min before injury on the exposed spinal cord followed by repeated doses of growth factors immediately before and 30 min after injury. Thereafter application of BDNF or IGF was carried out at every 1 h interval until sacrifice. Five hours after injury, the tissue pieces from the T9 segment were processed for nNOS immunostaining, edema and cell injury. Untreated injured rats showed a profound upregulation of nNOS which was most pronounced in the nerve cells of the ipsilateral side. A marked increase in the blood-spinal cord barrier (BSCB) permeability to 125I-albumin, water content and cell injury in these perifocal segments was also found. Pretreatment with BDNF and IGF significantly reduced the upregulation of nNOS in the spinal cord. This effect of the growth factors was most pronounced in the contralateral side. Rats treated with these neurotrophic factors showed much less signs of BSCB damage, edema and cell injury. These results suggest that BDNF and IGF pretreatment is neuroprotective in spinal cord injury and that these neurotrophic factors have the capacity to down regulate nNOS expression following trauma to the spinal cord. Our data provide new experimental evidences which suggest that BDNF and IGF may exert their potential neuroprotective effects probably via regulation of NOS activity.

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“…An increase in the serum concentrations of b-endorphin have also been observed in patients with heat stroke (13). Naltrexone, a wide-spectrum opioid-receptor antagonist with a strong anti-m -opioid receptor activity, has been demonstrated to attenuate the severity of heat stroke (7,8,10,14,15). However, the mechanism underlying the therapeutic effects of naltrexone on heat stroke remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Naltrexone Protects Against Hypotension, Hyperthermia, and β-Endorphin Overproduction During Heatstroke in the Rat

et al. 2005

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Abstract. Heat stroke is characterized by hyperthermia, arterial hypotension, decreased baroreflex sensitivity, and increased serum levels of b-endorphin. Whereas naltrexone may have therapeutic potential in heat stroke, the underlying mechanism remains unclear. We tested the hypothesis that naltrexone may attenuate heat stroke by reducing hyperthermia, hypotension, decreased baroreceptor sensitivity, and / or increased serum levels of b-endorphin. Heat stroke was induced by exposing the anesthetized adult Sprague-Dawley rats in an incubator at 43°C. The moment in which the mean arterial pressure dropped irreversibly from the peak level was taken as the onset of heat stroke. Control rats were exposed to 24°C. Mean arterial pressure, baroreceptor sensitivity, and maximal reflex bradycardia, after the onset of heat stroke, were all significantly lower than in control rats. However, rectal temperature and serum levels of bendorphin were all greater after the onset of heat stroke. Intravenous delivery of naltrexone (10 mg / kg) 20 min before the initiation of heat stress, but not immediately at the onset of heat stroke, significantly attenuated the above-mentioned reactions. Accordingly, naltrexone improved survival during heat stroke. These results suggest that naltrexone protects against hypotension and decrement of both baroreceptor sensitivity and maximal reflex bradycardia during heat stroke by reducing both hyperthermia and increment of serum b-endorphin and thus improves survival.

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Opioid Receptor Antagonists Attenuate Heat Stress‐Induced Reduction in Cerebral Blood Flow, Increased Blood‐Brain Barrier Permeability, Vasogenic Edema and Cell Changes in the Rat^a

Cited by 48 publications

References 30 publications

Pathophysiology of Blood-Spinal Cord Barrier in Traumatic Injury and Repair

Pathophysiology of Blood-Spinal Cord Barrier in Traumatic Injury and Repair

Brain derived neurotrophic factor and insulin like growth factor-1 attenuate upregulation of nitric oxide synthase and cell injury following trauma to the spinal cord

Naltrexone Protects Against Hypotension, Hyperthermia, and β-Endorphin Overproduction During Heatstroke in the Rat

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Opioid Receptor Antagonists Attenuate Heat Stress‐Induced Reduction in Cerebral Blood Flow, Increased Blood‐Brain Barrier Permeability, Vasogenic Edema and Cell Changes in the Rata

Cited by 48 publications

References 30 publications

Pathophysiology of Blood-Spinal Cord Barrier in Traumatic Injury and Repair

Pathophysiology of Blood-Spinal Cord Barrier in Traumatic Injury and Repair

Brain derived neurotrophic factor and insulin like growth factor-1 attenuate upregulation of nitric oxide synthase and cell injury following trauma to the spinal cord

Naltrexone Protects Against Hypotension, Hyperthermia, and β-Endorphin Overproduction During Heatstroke in the Rat

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Opioid Receptor Antagonists Attenuate Heat Stress‐Induced Reduction in Cerebral Blood Flow, Increased Blood‐Brain Barrier Permeability, Vasogenic Edema and Cell Changes in the Rat^a