Effects of HBO with reduction of iNOS and HIF -1α in motor neurons after transient spinal cord ischemia in rabbits

Background/Aims: Dexmedetomidine has beneficial effects on ischemia reperfusion (I/R) injury to the spinal cord, but the underlying mechanisms are not fully understood. This study investigated the effects and possible mechanisms of dexmedetomidine on blood-spinal cord barrier (BSCB) disruption induced by spinal cord I/R injury. Methods: Rats were intrathecally pretreated with dexmedetomidine or PBS control 30 minutes before undergoing 14-minute occlusion of aortic arch. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histological examination. The permeability of the BSCB was examined using Evans blue (EB) as a vascular tracer. The spinal cord edema was evaluated using the wet-dry method. The expression and localization of matrix metalloproteinase-9 (MMP-9), Angiopoietin-1 (Ang1) and Tie2 were assessed by western blot, real-time polymerase chain reaction, and immunofluorescence. Results: Intrathecal preconditioning with dexmedetomidine minimized the neuromotor dysfunction and histopathological deficits, and attenuated EB extravasation after spinal cord I/R injury. In addition, dexmedetomidine preconditioning suppressed I/R-induced increase in MMP-9. Finally, Dexmedetomidine preconditioning enhanced the Ang1-Tie2 system activity after spinal cord I/R injury. Conclusions: Dexmedetomidine preconditioning stabilized the BSCB integrity against spinal cord I/R injury by inhibition of MMP-9, and enhancing the Ang1-Tie2 system.

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Effect of coenzyme Q10 on spinal cord ischemia-reperfusion injury

Journal of Neurosurgery Spine ◽

10.3171/2014.12.spine14487 ◽

2015 ◽

Vol 22 (4) ◽

pp. 432-438 ◽

Cited By ~ 10

Author(s):

Jin-Young Hwang ◽

Seong-Won Min ◽

Young-Tae Jeon ◽

Jung-Won Hwang ◽

Sang-Heon Park ◽

...

Keyword(s):

Spinal Cord ◽

Reperfusion Injury ◽

Motor Neurons ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Coenzyme Q ◽

Spinal Cord Ischemia ◽

Neurological Function ◽

Saline Control ◽

Control Group

OBJECT Spinal cord ischemia remains a serious complication of thoracoabdominal aortic aneurysm surgery. Coenzyme Q10, a potent antioxidant, has been reported to exert a neuroprotective effect. In the present study, we evaluated the effect of coenzyme Q10 pretreatment on spinal cord ischemia-reperfusion injury. METHODS Male Sprague-Dawley rats were treated with either 300 mg/kg coenzyme Q10 (CoQ10 group, n = 12) or saline (control and sham groups, n = 12 for each group) for 5 days before ischemia. Spinal cord ischemia was induced in the control and CoQ10 groups. Neurological function was assessed using the Basso-Beattie-Bresnahan (BBB) motor rating scale until 7 days after reperfusion, and then the spinal cord was harvested for histopathological examinations and an evaluation of malondialdehyde level. RESULTS On post-reperfusion Day 1, the CoQ10 group showed higher BBB scores compared with those in the control group, although the difference was not significant. However, on Day 2, the CoQ10 group showed a significantly higher BBB score than the control group (14.0 [10.3–15.0] vs 8.0 [5.0–9.8], median [IQR], respectively; p = 0.021), and this trend was maintained until Day 7 (17.5 [16.0–18.0] vs 9.0 [6.5–12.8], respectively; p < 0.001). Compared with the control group, the CoQ10 group had more normal motor neurons (p = 0.003), fewer apoptotic changes (p = 0.003) and a lower level of tissue malondialdehyde (p = 0.024). CONCLUSIONS Pretreatment with 300 mg/kg coenzyme Q10 resulted in significantly improved neurological function and preservation of more normal motor neurons.

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Induction of Phosphorylated BAD in Motor Neurons After Transient Spinal Cord Ischemia in Rabbits

Advances in Understanding Aortic Diseases ◽

10.1007/978-4-431-99237-0_51 ◽

2009 ◽

pp. 271-275

Author(s):

Masahiro Sakurai ◽

Koji Abe ◽

Yasuto Itoyama ◽

Koichi Tabayashi

Keyword(s):

Spinal Cord ◽

Motor Neurons ◽

Spinal Cord Ischemia

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Survival and death-promoting events after transient spinal cord ischemia in rabbits: Induction of Akt and caspase3 in motor neurons

Journal of Thoracic and Cardiovascular Surgery ◽

10.1067/mtc.2003.112 ◽

2003 ◽

Vol 125 (2) ◽

pp. 370-377 ◽

Cited By ~ 60

Author(s):

Masahiro Sakurai ◽

Tatsuya Nagata ◽

Koji Abe ◽

Takashi Horinouchi ◽

Yasuto Itoyama ◽

...

Keyword(s):

Spinal Cord ◽

Motor Neurons ◽

Spinal Cord Ischemia

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Tat-p27 Ameliorates Neuronal Damage Reducing α-Synuclein and Inflammatory Responses in Motor Neurons After Spinal Cord Ischemia

Neurochemical Research ◽

10.1007/s11064-021-03392-0 ◽

2021 ◽

Author(s):

Woosuk Kim ◽

Hyun Jung Kwon ◽

Hyo Young Jung ◽

Kyu Ri Hahn ◽

Seung Myung Moon ◽

...

Keyword(s):

Spinal Cord ◽

Motor Neurons ◽

Inflammatory Responses ◽

Neuronal Damage ◽

Spinal Cord Ischemia

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The Activation of Spinal N-Methyl-d-Aspartate Receptors May Contribute to Degeneration of Spinal Motor Neurons Induced by Neuraxial Morphine After a Noninjurious Interval of Spinal Cord Ischemia

Anesthesia & Analgesia ◽

10.1213/01.ane.0000142123.63543.a6 ◽

2005 ◽

Vol 100 (2) ◽

pp. 327-334 ◽

Cited By ~ 11

Author(s):

Manabu Kakinohana ◽

Osamu Kakinohana ◽

Jong Hun Jun ◽

Martin Marsala ◽

Kenneth J. Davison ◽

...

Keyword(s):

Spinal Cord ◽

Motor Neurons ◽

Spinal Cord Ischemia ◽

Spinal Motor Neurons ◽

Spinal Motor

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Neuroprotection against Spinal Cord Ischemia–Reperfusion Injury Induced by Different Ischemic Postconditioning Methods

Anesthesiology ◽

10.1097/aln.0b013e3181bf1d93 ◽

2009 ◽

Vol 111 (6) ◽

pp. 1197-1205 ◽

Cited By ~ 36

Author(s):

Xiaojing Jiang ◽

Chunyu Ai ◽

Enyi Shi ◽

Yoshiki Nakajima ◽

Hong Ma

Keyword(s):

Spinal Cord ◽

Motor Neurons ◽

Spinal Cord Ischemia ◽

Ischemic Postconditioning ◽

Infrarenal Aorta ◽

Phosphatidylinositol 3 Kinase ◽

Neuroprotective Effects ◽

Significant Difference ◽

Lumbar Spinal ◽

Phosphatidylinositol 3

Background The authors compared the neuroprotective effects induced by two ischemic postconditioning methods and sought to determine the roles of phosphatidylinositol 3-kinase-Akt and extracellular signal-regulated kinase (ERK) in this neuroprotection. Methods Spinal cord ischemia was induced in rabbits by occlusion of the infrarenal aorta with a balloon catheter for 25 min. Postconditioning was accomplished by either five cycles of 1-min occlusion and 1-min reperfusion (standard postconditioning) or control of the perfusion pressure between 45 and 55 mmHg at the first 10 min of reperfusion (modified postconditioning). Motor function was assessed with the Tarlov score during a 28-day observation period. Histologic examination of lumbar spinal cords was performed. Expressions of Akt and ERK in the spinal cord were evaluated by Western blot. Results Compared with the controls, the two postconditioning methods markedly increased Tarlov scores 1, 3, 7, and 28 days after spinal cord ischemia and number of intact motor neurons in the lumbar spinal cord. No significant difference in Tarlov scores and number of intact motor neurons was detected between the two postconditioning method groups. The two postconditioning methods enhanced the expressions of phospho-Akt and phospho-ERK in spinal cords. The neuroprotective effects and the increases in phospho-Akt and phospho-ERK were abolished by administration of phosphatidylinositol 3-kinase-Akt inhibitor LY-294002 or ERK inhibitor PD-98059. Conclusions The two postconditioning methods possess comparable neuroprotective effects on the spinal cord and share a common molecular mechanism, in which phosphatidylinositol 3-kinase and ERK pathways play crucial roles.

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Intrathecal Injection of Hepatocyte Growth Factor Gene-modified Marrow Stromal Cells Attenuates Neurologic Injury Induced by Transient Spinal Cord Ischemia in Rabbits

Anesthesiology ◽

10.1097/aln.0b013e3181f6970d ◽

2010 ◽

Vol 113 (5) ◽

pp. 1109-1117 ◽

Cited By ~ 9

Author(s):

Enyi Shi ◽

Xiaojing Jiang ◽

Lingling Wang ◽

Satoshi Akuzawa ◽

Yoshiki Nakajima ◽

...

Keyword(s):

Spinal Cord ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Motor Neurons ◽

Stromal Cells ◽

Spinal Cord Ischemia ◽

Intrathecal Injection ◽

Marrow Stromal Cells ◽

Infrarenal Aorta ◽

Hepatocyte Growth

Background Our previous studies showed that transfer of hepatocyte growth factor (HGF) gene or transplantation of marrow stromal cells (MSCs) remarkably attenuated neurologic injuries after spinal cord ischemia. We sought to investigate a novel neuroprotective strategy of transplantation of human HGF gene-modified MSCs on ischemic spinal cords. Methods Human HGF gene was transferred into MSCs in vitro. The HGF gene-modified MSCs were transplanted by means of intrathecal injection. Two days later, spinal cord ischemia was induced by occlusion of the infrarenal aorta with a balloon catheter for 40 or 50 min. Hind-limb motor function was assessed during a 14-day recovery period with Tarlov criteria, and then histologic examination was performed. Results Human HGF was detected in the cerebrospinal fluid from 2 to 16 days after transplantation of HGF gene-modified MSCs. Compared with the controls, transplantation of HGF gene-modified MSCs or MSCs alone significantly improved the Tarlov scores 1, 2, 7, and 14 days after spinal cord ischemia of 40 or 50 min (P < 0.01, respectively) and increased the number of intact motor neurons in the lumbar spinal cord (P < 0.01, respectively). When the ischemic period was extended to 50 min, the Tarlov scores and the number of intact motor neurons of rabbits transplanted with HGF gene-modified MSCs were markedly higher than those of the rabbits transplanted with MSCs only (P < 0.05, respectively). Conclusions Transplantation of HGF gene-modified MSCs induces powerful neuroprotection on spinal cords against ischemia-reperfusion injury and is more therapeutically efficient than transplantation of MSCs only.

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