Combined use of an epidural cooling catheter and systemic moderate hypothermia enhances spinal cord protection against ischemic injury in rabbits

Inoué, Shinya; Mori, Atsuo; Shimizu, Hideyuki; Yoshitake, Akihiro; Tashiro, Ryoichi; Kabei, Nobuyuki; Yozu, Ryohei

doi:10.1016/j.jtcvs.2012.11.040

Cited by 26 publications

(18 citation statements)

References 13 publications

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“…25 To count the survival neurons, animals (n = 5 per group) were killed, and transverse sections of the injured spinal cord were used to stain neurons with Nissl. The T8-T11 longitudinal spinal cord sections from each group were stained with HE according to standard protocols and observed under bright field microscope.…”

Section: Histological Analysismentioning

confidence: 99%

Wnt4‐modified NSC transplantation promotes functional recovery after spinal cord injury

Peng

Long

et al. 2019

The FASEB Journal

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Spinal cord injury (SCI) can lead to severe motor and sensory dysfunction, yet there are no effective therapies currently due to the failure of reconstructing the interruption of the neuroanatomical circuit. While neural stem cell (NSC) transplantation has been considered a potential strategy to repair the neural circuit after SCI, the efficacy of this strategy remains unproven. The main reason is that most of the transplanted NSC differentiates into astrocyte rather than neuron in the microenvironment of SCI. Our results demonstrated that Wnt4 significantly promotes the differentiation of NSC into neuron by activating both β‐catenin and MAPK/JNK pathways and suppressing the activation of Notch signaling, which is acknowledged as prevention of NSC differentiation into neuron, through downregulating NICD expression, translocating and preventing the combination of NICD and RbpJ in nucleus. In addition, Wnt4 rescues the negative effect of Jagged, the ligand of Notch signaling, to promote neuronal differentiation. Moreover, in vivo study, transplantation of Wnt4‐modified NSC efficaciously repairs the injured spinal cord and recovers the motor function of hind limbs after SCI. This study sheds new light into mechanisms that Wnt4‐modified NSC transplantation is sufficient to repair the injured spinal cord and recover the motor dysfunction after SCI.

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Section: Histological Analysismentioning

confidence: 99%

Wnt4‐modified NSC transplantation promotes functional recovery after spinal cord injury

Peng

Long

et al. 2019

The FASEB Journal

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“…These include epidural placement of cooling catheter (Inoue, et al, 2012), passive heat dissipation (D’Ambrosio, et al, 2013), local cold fluid infusion (Chen, et al, 2013) and extracorporeal veno-venous blood cooling (Kuboi, et al, 2013, Testori, et al, 2013). Recently, pharmacologically induced hypothermia (PIH) or drug-induced hypothermia (DIH) has drawn increased attention due to its target specific, receptor/channel mediated effect and effective inductions of regulated hypothermia (Muzzi, et al, 2013, Tupone, et al, 2013, Zhang, et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats

Wei

Espinera

et al. 2015

Experimental Neurology

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Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A six-hour hypothermic treatment, providing an overall 2-3°C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15 min or 2 hr after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and Caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the HPI201 treated group exhibited improved functional recovery after TBI versus controls. These data support that PIH therapy using our NTR agonist is effective in reducing neuronal and BBB damage, attenuating inflammatory response and detrimental cellular signaling, and promoting functional recovery after TBI in the developing brain, supporting its potential for further evaluation towards clinical development.

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“…Regional or systemic hypothermia of the cord is also theoretically believed to be protective. Although excellent results have been reported, complications associated with general deep hypothermia [45,46] and complexity of the catheter systems [47,48] in epidural space negate the general use of hypothermia. Numerous pharmacological agents, such as papaverine, naloxone, corticosteroids, oxygen radical scavenger [49], prostaglandin, excitatory amino acid antagonist, and even ''a non-specific flu medicine'' have been tried.…”

Section: Thoracoabdominal Aortic Aneurysmmentioning

confidence: 99%

Surgery for thoracic aortic disease in Japan: evolving strategies toward the growing enemies

Okita

2014

Gen Thorac Cardiovasc Surg

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Combined use of an epidural cooling catheter and systemic moderate hypothermia enhances spinal cord protection against ischemic injury in rabbits

Abstract: Epidural cooling catheter combined with systemic moderate hypothermia produced additive cooling ability and protected the spinal cord against ischemia in rabbits more effectively than either intervention alone.

Cited by 26 publications

References 13 publications

Wnt4‐modified NSC transplantation promotes functional recovery after spinal cord injury

Wnt4‐modified NSC transplantation promotes functional recovery after spinal cord injury

Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats

Surgery for thoracic aortic disease in Japan: evolving strategies toward the growing enemies

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