Efficacy of mild hypothermia (35°C) and moderate hypothermia (33°C) with and without magnesium when administered 30min post-reperfusion after 90min of middle cerebral artery occlusion in Spontaneously Hypertensive rats

Campbell, Kym; Knuckey, Neville W.; Brookes, Laura M.; Meloni, Bruno P.

doi:10.1016/j.brainres.2013.01.038

Cited by 13 publications

(5 citation statements)

References 32 publications

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“…For instance, TBI victims suffer from brain oxygen depletion, vasogenic edema, and secondary injury signals including reactive oxygen species, exacerbated activated MHCII+ cells, astrogliosis and pro-inflammatory cytokines such as, but not limited to, IL-1beta, TNF-alpha which can accumulate in the area of injury leading to decreased survival of transplanted adult stem cells [11], [25], [26]. The use of combined therapies stands as a promising technique to overcome molecular aberrations while enhancing the adult stem cells' therapeutic potential in chronic TBI [27], [28].…”

Section: Introductionmentioning

confidence: 99%

Combination Therapy of Human Umbilical Cord Blood Cells and Granulocyte Colony Stimulating Factor Reduces Histopathological and Motor Impairments in an Experimental Model of Chronic Traumatic Brain Injury

et al. 2014

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Traumatic brain injury (TBI) is associated with neuro-inflammation, debilitating sensory-motor deficits, and learning and memory impairments. Cell-based therapies are currently being investigated in treating neurotrauma due to their ability to secrete neurotrophic factors and anti-inflammatory cytokines that can regulate the hostile milieu associated with chronic neuroinflammation found in TBI. In tandem, the stimulation and mobilization of endogenous stem/progenitor cells from the bone marrow through granulocyte colony stimulating factor (G-CSF) poses as an attractive therapeutic intervention for chronic TBI. Here, we tested the potential of a combined therapy of human umbilical cord blood cells (hUCB) and G-CSF at the acute stage of TBI to counteract the progressive secondary effects of chronic TBI using the controlled cortical impact model. Four different groups of adult Sprague Dawley rats were treated with saline alone, G-CSF+saline, hUCB+saline or hUCB+G-CSF, 7-days post CCI moderate TBI. Eight weeks after TBI, brains were harvested to analyze hippocampal cell loss, neuroinflammatory response, and neurogenesis by using immunohistochemical techniques. Results revealed that the rats exposed to TBI treated with saline exhibited widespread neuroinflammation, impaired endogenous neurogenesis in DG and SVZ, and severe hippocampal cell loss. hUCB monotherapy suppressed neuroinflammation, nearly normalized the neurogenesis, and reduced hippocampal cell loss compared to saline alone. G-CSF monotherapy produced partial and short-lived benefits characterized by low levels of neuroinflammation in striatum, DG, SVZ, and corpus callosum and fornix, a modest neurogenesis, and a moderate reduction of hippocampal cells loss. On the other hand, combined therapy of hUCB+G-CSF displayed synergistic effects that robustly dampened neuroinflammation, while enhancing endogenous neurogenesis and reducing hippocampal cell loss. Vigorous and long-lasting recovery of motor function accompanied the combined therapy, which was either moderately or short-lived in the monotherapy conditions. These results suggest that combined treatment rather than monotherapy appears optimal for abrogating histophalogical and motor impairments in chronic TBI.

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Section: Introductionmentioning

confidence: 99%

Combination Therapy of Human Umbilical Cord Blood Cells and Granulocyte Colony Stimulating Factor Reduces Histopathological and Motor Impairments in an Experimental Model of Chronic Traumatic Brain Injury

et al. 2014

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“…To this end, we revisit the utility of hypothermia, now moving from the moderate hypothermia used in our previous studies to mild hypothermia (35°C) to determine whether a relatively modest drop in temperature can exert any protective effects, which, obviously, could prove of clinical utility. [25][26][27] Additionally, to better understand the potential involvement of damaging oxygen radicals in the process of repetitive injury and the benefits of their therapeutic attenuation, we revisit our previous studies, 22,23 now using postrepetitive administration of either superoxide dismutase (SOD) or Tempol, based upon the recognition that SOD will dismutate the superoxide anion, whereas Tempol serves as a nitroxide antioxidant that decomposes both the superoxide radical and the peroxynitrite-derived radical species, all of which have been implicated in the pathogenesis of various forms of axonal and vascular change after TBI. [28][29][30][31][32][33] In the current communication, we report that the use of even mild hypothermia (35°C) exerts significant axonal and vascular protection when the hypothermia is initiated relatively late (1 h) after repetitive injury, with both SOD and Tempol providing comparable protection when administered in the same time frame.…”

mentioning

confidence: 99%

Evidence for the Therapeutic Efficacy of Either Mild Hypothermia or Oxygen Radical Scavengers after Repetitive Mild Traumatic Brain Injury

Miyauchi

Wei²,

Povlishock³

2014

Journal of Neurotrauma

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Repetitive brain injury, particularly that occurring with sporting-related injuries, has recently garnered increased attention in both the clinical and public settings. In the laboratory, we have demonstrated the adverse axonal and vascular consequences of repetitive brain injury and have demonstrated that moderate hypothermia and/or FK506 exerted protective effects after repetitive mild traumatic brain injury (mTBI) when administered within a specific time frame, suggesting a range of therapeutic modalities to prevent a dramatic exacerbation. In this communication, we revisit the utility of targeted therapeutic intervention to seek the minimal level of hypothermia needed to achieve protection while probing the role of oxygen radicals and their therapeutic targeting. Male Sprague-Dawley rats were subjected to repetitive mTBI by impact acceleration injury. Mild hypothermia (35°C, group 2), superoxide dismutase (group 3), and Tempol (group 4) were employed as therapeutic interventions administered 1 h after the repetitive mTBI. To assess vascular function, cerebral vascular reactivity to acetylcholine was evaluated 3 and 4 h after the repetitive mTBI, whereas to detect the burden of axonal damage, amyloid precursor protein (APP) density in the medullospinal junction was measured. Whereas complete impairment of vascular reactivity was observed in group 1 (without intervention), significant preservation of vascular reactivity was found in the other groups. Similarly, whereas remarkable increase in the APP-positive axon was observed in group 1, there were no significant increases in the other groups. Collectively, these findings indicate that even mild hypothermia or the blunting free radical damage, even when performed in a delayed period, is protective in repetitive mTBI.

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“…From mouse models, the thermoregulatory profile during passive heat stress has been characterized as a triphasic pattern, with an initial linear core temperature (T c ) increase, a subsequent equilibrium plateau, and a final rapid progression to HS (5). Prolonged physical activity in hot and humid environmental conditions increases the risk of HS (6,7). During exercise, a significant amount of extra heat is released from active skeletal muscles.…”

Section: Introductionmentioning

confidence: 99%

Physical Effort Affects Heatstroke Thermoregulatory Response and Mortality in Rats

Geng¹,

Peng

Liu

et al. 2015

Shock

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Animals suffering from heatstroke (HS) after physical effort may have different heat-related core temperature (Tc) responses compared with passive HS. In the present study, conscious and unrestrained rats were exposed to ambient temperature (Ta) of 39.5°C ± 0.2°C with or without running (run-heated or rest-heated, respectively) until HS onset, which was defined as the systolic blood pressure starting to drop. In comparison with rest-heated rats, run-heated rats had a significantly shorter latency of HS onset. Physical effort did not have significant influence on hyperthermia severity (43.3°C ± 0.2°C at rest-heated, and 43.4°C ± 0.2°C at run-heated), but it could significantly decrease the thermal load to develop HS (315.1°C ± 37.3°C·min for rest-heated, and 133.5 ± 21.4 °C·min for run-heated). Working component during heat exposure may contribute to a decreased survival rate of HS (46.9% at rest-heated and 31.3% at run-heated). Impaired heat dissipation during recovery may be responsible for relative poor survival of run-heated rats. In both groups, survival was affected by Tc at HS onset and thermal area. Hypothermia (Tc <35°C) developed after HS onset, with no significant difference in Tc,min between the rest-heated and run-heated groups. These thermoregulatory responses to HS after physical effort may provide insight into HS pathophysiology.

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Efficacy of mild hypothermia (35°C) and moderate hypothermia (33°C) with and without magnesium when administered 30min post-reperfusion after 90min of middle cerebral artery occlusion in Spontaneously Hypertensive rats

Cited by 13 publications

References 32 publications

Combination Therapy of Human Umbilical Cord Blood Cells and Granulocyte Colony Stimulating Factor Reduces Histopathological and Motor Impairments in an Experimental Model of Chronic Traumatic Brain Injury

Combination Therapy of Human Umbilical Cord Blood Cells and Granulocyte Colony Stimulating Factor Reduces Histopathological and Motor Impairments in an Experimental Model of Chronic Traumatic Brain Injury

Evidence for the Therapeutic Efficacy of Either Mild Hypothermia or Oxygen Radical Scavengers after Repetitive Mild Traumatic Brain Injury

Physical Effort Affects Heatstroke Thermoregulatory Response and Mortality in Rats

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