Topical Application of Insulin Like Growth Factor-1 Reduces Edema and Upregulation of Neuronal Nitric Oxide Synthase Following Trauma to the Rat Spinal Cord

Sharma, Hari Shanker; Nyberg, Fred; Gordh, Torsten; Alm, P.; Westman, Jan

doi:10.1007/978-3-7091-6837-0_40

Cited by 52 publications

(24 citation statements)

References 14 publications

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“…High levels of expression achieved via AAV2 delivery most likely provides a sufficient level of local IGF-1 to overcome loss of IGF-1 signaling associated with disease. The present results coincide with previous studies that have shown that IGF-1 exerts pro-survival effects specifically on motor neurons: 1) in dissociated culture [57], 2) in the organotypic spinal cord model of excitotoxicity [19], 3) during developmental programmed cell death [37], 4) following spinal cord ischemia [44], spinal transaction [51], peripheral axotomy [38], crush injury [47] and root avulsion [29], 5) in the wobbler mouse [30] and in the SOD1 mouse [20,34].…”

Section: Therapeutic Actions Of Igf-1 In Alssupporting

confidence: 91%

Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALS

Lepore

Haenggeli

Gasmi³

et al. 2007

Brain Research

113

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The potent neuroprotective activities of neurotrophic factors, including insulin-like growth factor 1 (IGF-1), make them promising candidates for treatment of amyotrophic lateral sclerosis (ALS). In an effort to maximize rate of motor neuron transduction, achieve high levels of spinal IGF-1, and thus enhance therapeutic benefit, we injected an adeno-associated virus 2 (AAV2)-based vector encoding human IGF-1 (CERE-130) into lumbar spinal cord parenchyma of SOD1 G93A mice. We observed robust and long-term intraspinal IGF-1 expression and partial rescue of lumbar spinal cord motor neurons, as well as sex-specific delayed disease onset, weight loss, decline in hindlimb grip strength and increased animal survival.

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Section: Therapeutic Actions Of Igf-1 In Alssupporting

confidence: 91%

Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALS

Lepore

Haenggeli

Gasmi³

et al. 2007

Brain Research

113

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“…5 D.c). The BSCB permeability to iodine and the increased water content in the T9 and T12 segment were significantly reduced ( [46,47,221] ; Fig. 7A).…”

Section: Neuroprotective Effects Of Neurotrophins In Scimentioning

confidence: 93%

“…6). In addition, the nerve cell, glial cell and myelin damage are examined using specific markers at 5 h after injury [32,46,70,72,99,[115][116][117][217][218][219][220][221][222].…”

Section: Neuronal Glial and Axonal Changes In Scimentioning

confidence: 99%

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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“…Spinal cord injured rats exhibited marked increase in the blood-spinal cord barrier (BSCB) permeability to 125I-albumin and water content in T9 and T12 perifocal segments (Sharma et al, 1996). Pretreatment with neurotrophic factors significantly attenuated the extravasation of iodine across the BSCB (Sharma et al, unpublished observations) and reduced the edema formation as seen by changes in the spinal cord water content (Fig.…”

Section: Effect Of Neurotrophins On Edema and Microvascular Permeabilitymentioning

confidence: 94%

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

Amino Acids

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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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Topical Application of Insulin Like Growth Factor-1 Reduces Edema and Upregulation of Neuronal Nitric Oxide Synthase Following Trauma to the Rat Spinal Cord

Cited by 52 publications

References 14 publications

Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALS

Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALS

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

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