The effect of hypothermia on sensory-motor function and tissue sparing after spinal cord injury

Grulova, Ivana; Slovinská, Lucia; Nagyova, Miriam; Čížek, Milan; Cizkova, Dasa

doi:10.1016/j.spinee.2013.06.073

Cited by 34 publications

(26 citation statements)

References 66 publications

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“…A similar relationship may also be present after SCI (unpublished data). The inflammasome as a target for post-traumatic therapeutic hypothermia Post-traumatic therapeutic hypothermia is a promising therapeutic intervention to treat patients with traumatic brain and spinal cord injury (Ahmad et al, 2013; Grulova et al, 2013). Animal studies have shown that the neuroprotective effects associated with hypothermia are vast (Ahmad et al, 2013; Bell et al, 1998; Horiguchi et al, 2002) and include anti-inflammatory effects, mediated in part through inhibition of inflammasomes (Gu et al, 2014).…”

Section: Pattern Recognition Receptors In the Cnsmentioning

confidence: 99%

Pattern recognition receptors and central nervous system repair

Kigerl

Vaccari

Dietrich

et al. 2014

Experimental Neurology

396

299

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Pattern recognition receptors (PRRs) are part of the innate immune response and were originally discovered for their role in recognizing pathogens by ligating specific pathogen associated molecular patterns (PAMPs) expressed by microbes. Now the role of PRRs in sterile inflammation is also appreciated, responding to endogenous stimuli referred to as “damage associated molecular patterns” (DAMPs) instead of PAMPs. The main families of PRRs include Toll-like receptors (TLRs), Nod-like receptors (NLRs), RIG-like receptors (RLRs), AIM2-like receptors (ALRs), and C-type lectin receptors. Broad expression of these PRRs in the CNS and the release of DAMPs in and around sites of injury suggest an important role for these receptor families in mediating post-injury inflammation. Considerable data now show that PRRs are among the first responders to CNS injury and activation of these receptors on microglia, neurons, and astrocytes triggers an innate immune response in the brain and spinal cord. Here we discuss how the various PRR families are activated and can influence injury and repair processes following CNS injury.

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Section: Pattern Recognition Receptors In the Cnsmentioning

confidence: 99%

Pattern recognition receptors and central nervous system repair

Kigerl

Vaccari

Dietrich

et al. 2014

Experimental Neurology

396

299

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“…Compared to previous studies, the present study has important novelties. First, while most studies have used target hypothermia temperatures of 32°C-33°C-34°C (Khan et al, 2007;Kang et al, 2010;Grulova et al, 2013;Saito et al, 2013), a lower target temperature of 30°C was used in our experiment. This temperature was considered close to that of therapeutic general hypothermia (32°C) induced 2 hours after contusive SCI .…”

Section: Discussionmentioning

confidence: 99%

“…This temperature was considered close to that of therapeutic general hypothermia (32°C) induced 2 hours after contusive SCI . Second, local hypothermia was prolonged to meet the needs of clinical application to desired durations of 5 and 8 hours (Lotocki et al, 2011;Grulova et al, 2013;Saito et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Prolonged Local Hypothermia Has No Long-Term Adverse Effect on the Spinal Cord

Vipin

Kortelainen

Al‐Nashash

et al. 2015

Therapeutic Hypothermia and Temperature Management

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Hypothermia is known to be neuroprotective and is one of the most effective and promising first-line treatments for central nervous system (CNS) trauma. At present, induction of local hypothermia, as opposed to general hypothermia, is more desired because of its ease of application and safety; fewer side effects and an absence of severe complications have been noted. Local hypothermia involves temperature reduction of a small and specific segment of the spinal cord. Our group has previously shown the neuroprotective effect of short-term, acute moderate general hypothermia through improvements in electrophysiological and motor behavioral assessments, as well as histological examination following contusive spinal cord injury (SCI) in rats. We have also shown the benefit of using short-term local hypothermia versus short-term general hypothermia post-acute SCI. The overall neuroprotective benefit of hypothermia can be categorized into three main components: (1) induction modality, general versus local, (2) invasive, semi-invasive or noninvasive, and (3) duration of hypothermia induction. In this study, a series of experiments were designed to investigate the feasibility, long-term safety, as well as eventual complications and side effects of prolonged, semi-invasive, moderate local hypothermia (30°C±0.5°C for 5 and 8 hours) in rats with uninjured spinal cord while maintaining their core temperature at 37°C±0.5°C. The weekly somatosensory evoked potential and motor behavioral (Basso, Beattie and Bresnahan) assessments of rats that underwent 5 and 8 hours of semi-invasive local hypothermia, which revealed no statistically significant changes in electrical conductivity and behavioral outcomes. In addition, 4 weeks after local hypothermia induction, histological examination showed no anatomical damages or morphological changes in their spinal cord structure and parenchyma. We concluded that this method of prolonged local hypothermia is feasible, safe, and has the potential for clinical translation.

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“…Sections were finally washed in TBS and coverslipped in Enthelan. Similarly serial sagittal sections (n = 5) were stained with Luxol Fast Blue to determine the length and cavity size area 40 . Schematic concept of dissected spinal cord segments consisting of rostral (Th5-7), central (Th8-9), caudal (Th10-12) segments processed for immunohistochemical analyses is included in ( Supplementary Figure 3 ).…”

Section: Methodsmentioning

confidence: 99%

Delivery of Alginate Scaffold Releasing Two Trophic Factors for Spinal Cord Injury Repair

Grulova

Slovinská

Blasko

et al. 2015

Sci Rep

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Spinal cord injury (SCI) has been implicated in neural cell loss and consequently functional motor and sensory impairment. In this study, we propose an alginate -based neurobridge enriched with/without trophic growth factors (GFs) that can be utilized as a therapeutic approach for spinal cord repair. The bioavailability of key GFs, such as Epidermal Growth factor (EGF) and basic Fibroblast Growth Factor (bFGF) released from injected alginate biomaterial to the central lesion site significantly enhanced the sparing of spinal cord tissue and increased the number of surviving neurons (choline acetyltransferase positive motoneurons) and sensory fibres. In addition, we document enhanced outgrowth of corticospinal tract axons and presence of blood vessels at the central lesion. Tissue proteomics was performed at 3, 7 and 10 days after SCI in rats indicated the presence of anti-inflammatory factors in segments above the central lesion site, whereas in segments below, neurite outgrowth factors, inflammatory cytokines and chondroitin sulfate proteoglycan of the lectican protein family were overexpressed. Collectively, based on our data, we confirm that functional recovery was significantly improved in SCI groups receiving alginate scaffold with affinity-bound growth factors (ALG +GFs), compared to SCI animals without biomaterial treatment.

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The effect of hypothermia on sensory-motor function and tissue sparing after spinal cord injury

Cited by 34 publications

References 66 publications

Pattern recognition receptors and central nervous system repair

Pattern recognition receptors and central nervous system repair

Prolonged Local Hypothermia Has No Long-Term Adverse Effect on the Spinal Cord

Delivery of Alginate Scaffold Releasing Two Trophic Factors for Spinal Cord Injury Repair

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