Human Umbilical Cord Blood-Derived Cd34+ Cells Cause Attenuation of Multiorgan Dysfunction During Experimental Heatstroke

Chen, Sheng-Hsien; Chang, Feng-Cheng; Chang, Hsiu-Kang; Chen, Wei‐Chun; Huang, Kuo‐Feng; Lin, Mao‐Tsun

doi:10.1097/01.shk.0000248593.71388.40

Cited by 37 publications

(25 citation statements)

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“…Based on these observations together, KYNA might cause the attenuation of heat-induced multiple organ dysfunction via the mechanisms of the glycine site of NMDA and of the α-7 nicotinic acetylcholine receptors as well as a ligand for the orphan G-protein coupled receptor, GPR35. Altered blood-brain-barrier (BBB) permeability and brain injury occurred during heatstroke in rats [29] . In addition, human umbilical cord derived CD34 + cells were found to be able to pass into the hyperthermic brain to attenuate heat-induced brain injury and damage in rats [30] .…”

Section: Discussionmentioning

confidence: 99%

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke

Hsieh

Chen

Yeh³

et al. 2011

Acta Pharmacol Sin

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IntroductionHeatstroke is defined as a form of excessive hyperthermia (>40 °C) associated with a systemic inflammatory response that leads to multi-organ dysfunction in which central nervous system (CNS) disorders such as delusion, convulsion and coma predominate [1] . Our recent results have demonstrated that heatstroke rodents display hypotension, systemic inflammatory responses, hypothalamic ischemia and neuronal damage, and multi-organ dysfunction [2][3][4] .Kynurenic acid (KYNA) or its metabolic precursor L-kynurenine may be of therapeutic value in neurodegenerative diseased models [5,6] . For example, systemically administered high doses of KYNA had a neuroprotective effect in the gerbil model of global ischemia [7] . Both the homocysteine-induced impairment of endothelial cells [8] and the motility and inflammatory activation in the early phase of acute experimental colitis in the rat [9] were significantly reduced by administration of KYNA. The aim of this study was to investigate whether the heatstroke induced hypotension, systemic inflammatory responses, hypothalamic ischemia and damage, and multiorgan dysfunction could be attenuated by KYNA preconditioning. Accordingly, the temporal profiles of the apoptotic cell numbers of spleen, kidney, liver, lung, and hypothalamus, Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke Aim: To assess whether systemic delivery of kynurenic acid improves the outcomes of heatstroke in rats. Methods: Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline 0.3 mL/kg rat weight) or kynurenic acid (30-100 mg in 0.3 mL saline/kg) 4 h before the start of thermal experiments. They were exposed to an ambient temperature of 43 ºC for 68 min to induce heatstroke. Another group of rats were exposed to room temperature (26 ºC) and used as normothermic controls. Their core temperatures, mean arterial pressures, serum levels of systemic inflammatory response molecules, hypothalamic values of apoptotic cells and neuronal damage scores, and spleen, liver, kidney and lung values of apoptotic cells were determined. Results: The survival time values during heatstroke for vehicle-treated rats were decreased from the control values of 475-485 min to new values of 83-95 min. Treatment with KYNA (30-100 mg/kg, iv) 4 h before the start of heat stress significantly and dose-dependently decreased the survival time to new values of 152-356 min (P<0.05). Vehicle-treated heatstroke rats displayed hypotension, hypothalamic neuronal degeneration and apoptosis, increased serum levels of tunor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and interleukin-10 (IL-10), and spleen, liver, kidney, and lung apoptosis. KYNA preconditioning protected against hypotension but not hyperthermia and attenuated hypothalamic neuronal degeneration and apoptosis during heatstroke. KYNA preconditioning attenuated spleen, kidney, liver, and lung apoptosis and up-regulated serum IL-10 levels but down-regulated serum TNF-α and ICAM-1 lev...

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Section: Discussionmentioning

confidence: 99%

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke

Hsieh

Chen

Yeh³

et al. 2011

Acta Pharmacol Sin

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“…During these studies it was observed that the administration of FK506, at concentrations far below that required for its immunosuppressant function (5 mg/kg/day down to 0.05 mg/kg/day for 4 weeks), influenced axon regeneration. FK506 (1) induces a 2-fold increase in the number of axons that regenerate, (2) increases the speed of axon regeneration across 4 cm gaps, (3) increases the number of myelinated axons by 40% , (4) significantly increases myelin thickness, (5) increases the specificity of sensory and motor target reinnervation, and (6) increases the extent of neurological recovery [346][347][348][349][350][351][352][353][354][355][356].…”

Section: Immunosuppressantsmentioning

confidence: 99%

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

Kuffler¹

2015

Int J Neurorehabilitation Eng

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Repairing Peripheral Nerves following Traumas Nerve crushWithin several days of crushing a peripheral nerve, the injured axons begin to regenerate through their distal pathway until they reach their original targets with which they restore neurological function. The larger the number of axons that regenerate through the distal nerve, the greater the extent of neurological recovery [1][2][3]. The number of axons that regenerate, and thus neurological recovery, is influenced by the physiological state of the distal denervated nerve pathway [4][5][6][7].Following a peripheral nerve crush, the injured axons begin to regenerate within 2 days of injury [8]. They may regenerate to their targets through their original pathway in association with and promoted by its Schwann cells, the neurotrophic factors they release, and the Schwann cell extracellular matrix [1,4,[9][10][11][12][13][14]. Thus, the distal nerve provides a simple means for promoting and directing the regenerating axons to their original targets [15][16][17][18]. However, when a nerve has a gap, the gap must be bridged with a material that is permissive to and promotes axon regeneration across the entire gap to reach the distal nerve stump, through which the axons must then be able to regenerate.The Schwann cells in the denervated distal nerve release neurotrophic factors that promote axon regeneration, but also release extracellular matrix components that promote and inhibit axon regeneration [19][20][21][22][23][24][25][26]. Thus, regeneration through the distal nerve is a balance of the influences of factors that both promote and inhibit regeneration. If the Schwann cells are present, such as after a simple nerve crush, virtually 100% of the axons regenerate and they innervate all the denervated synaptic sites. If the Schwann cells within the distal nerve pathway are killed, leaving only the extracellular matrix intact, the number of axons that regenerates to their targets decreases by 94%. This is because the factors required to trigger the regenerating axons to branch at extracellular matrix branch points are missing, axons do not branch, and therefore each axon reinnervates only a single denervated muscle fiber. Thus, Schwann cells along the distal nerve pathway and a AbstractFollowing a peripheral nerve crush, or when a peripheral the nerve is transected and the nerve stumps anastomosed, neurological recovery is generally excellent. This is because the axons merely have to regenerate through the distal portion of the nerve through the existing extracellular matrix of the denervated Schwann cells that direct and promote them to their distant denervated motor and sensory targets. However, when a length of a peripheral nerve is destroyed, and anastomosis is not possible, the standard surgical repair technique is to graft a length/s of autologous sensory nerve into the gap. Neurological recovery is generally good if the nerve gap is <2 cm in length, the repair is performed <4 months post trauma, and the patients are <25 years of age. Because the nerve ...

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“…Core temperature (Tco) was monitored continuously by a thermocouple inserted into the rectum, while both mean arterial pressure (MAP) and heart rate (HR) were continuously monitored with a pressure transducer. For measurement of intracranial pressure (ICP), the animals were positioned in a stereotaxic apparatus (Kopf 1406; Grass Instrument, Quincy, MA, USA) to insert probes for a Statham P23AC transducer via 20-gauge stainless-steel-needled probe (diameter, 0.90 mm; length, 38 cm), which was introduced into the right cerebral ventricle according to the stereotaxic coordinates of Paxinos and Watson (9).…”

Section: Surgery and Physiologic Parameter Monitoringmentioning

confidence: 99%

“…Heatstroke was induced by putting the animals in a folded heating pad of 43°C controlled by circulating hot water. The instant at which the MAP dropped to 25 mmHg from the peak level was taken as the onset of heatstroke (8,9). After the onset of heatstroke, the heating pad was removed and the animals were allowed to recover at room temperature (24°C).…”

Section: Induction Of Heatstrokementioning

confidence: 99%

Human Umbilical Cord Blood–Derived CD34+ Cells Can Be Used as a Prophylactic Agent for Experimental Heatstroke

Hwang¹,

Chen²,

Lin³

et al. 2008

J Pharmacol Sci

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Abstract. We attempted to assess the prophylactic effect of human umbilical cord bloodderived CD34+ cells in experimental heatstroke. Anesthetized rats, 1 day before heat stress, were divided into 2 major groups and given CD34 − cells (defined by 1 × 10 6 human cord blood lymphocytes and monocytes that contained <0.2% CD34 + cells) or CD34 + cells (defined by 1 × 10 6 human cord blood lymphocytes and monocytes that contained >95% CD34 + cells). They were exposed to ambient temperature of 43°C for 70 min to induce heatstroke. When the CD34 − cells-treated or untreated rats underwent heat stress, their survival time values were found to be 20 -24 min. Pretreatment with CD34+ cells significantly increased survival time (123 -351 min). As compared with normothermic controls, all CD34− cells-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, these heatstroke reactions all were significantly suppressed by CD34 + cells pretreatment. In addition, the levels of interlukin-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34 + cell administration during heatstroke. Our data indicate that human umbilical cord-derived CD34 + cells can be used as a prophylactic agent for experimental heatstroke.

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Human Umbilical Cord Blood-Derived Cd34+ Cells Cause Attenuation of Multiorgan Dysfunction During Experimental Heatstroke

Cited by 37 publications

References 50 publications

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

Human Umbilical Cord Blood–Derived CD34+ Cells Can Be Used as a Prophylactic Agent for Experimental Heatstroke

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