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Attenuation of circulatory shock and cerebral ischemia injury in heat stroke by combination treatment with dexamethasone and hydroxyethyl starch.

Yang TH, Shih MF, Wen YS, Ho WY, Leu KL, Wang MY, Liu CC - Exp Transl Stroke Med (2010)

Bottom Line: Concentrations of the ischemic and damage markers, dopamine, serotonin, and hydroxyl radical productions in corpus striatum, and the serum levels of interleukin-1 beta, tumor necrosis factor-alpha and malondialdehyde (MDA) were observed during heat stroke.After heat stroke, the rats displayed circulatory shock (arterial hypotension), decreased CBF, increased the serum levels of cytokines and MDA, increased cerebral striatal monoamines and hydroxyl radical productions release, and severe cerebral ischemia and neuronal damage compared with those of normothermic control rats.Our results suggest that the combination of a colloid substance with a volume-expanding effect and an anti-inflammatory agent may provide a better resuscitation solution for victims with heat stroke.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department and Institute of Cosmetic Science, Chia-Nan University of Pharmacy and Science, Tainan 71710, Taiwan. ccliu@mail.chna.edu.tw.

ABSTRACT

Background: Increased systemic cytokines and elevated brain levels of monoamines, and hydroxyl radical productions are thought to aggravate the conditions of cerebral ischemia and neuronal damage during heat stroke. Dexamethasone (DXM) is a known immunosuppressive drug used in controlling inflammation, and hydroxyethyl starch (HES) is used as a volume-expanding drug in cerebral ischemia and/or cerebral injury. Acute treatment with a combined therapeutic approach has been repeatedly advocated in cerebral ischemia experiments. The aim of this study is to investigate whether the combined agent (HES and DXM) has beneficial efficacy to improve the survival time (ST) and heat stroke-induced cerebral ischemia and neuronal damage in experimental heat stroke.

Methods: Urethane-anesthetized rats underwent instrumentation for the measurement of colonic temperature, mean arterial pressure (MAP), local striatal cerebral blood flow (CBF), heart rate, and neuronal damage score. The rats were exposed to an ambient temperature (43 degrees centigrade) to induce heat stroke. Concentrations of the ischemic and damage markers, dopamine, serotonin, and hydroxyl radical productions in corpus striatum, and the serum levels of interleukin-1 beta, tumor necrosis factor-alpha and malondialdehyde (MDA) were observed during heat stroke.

Results: After heat stroke, the rats displayed circulatory shock (arterial hypotension), decreased CBF, increased the serum levels of cytokines and MDA, increased cerebral striatal monoamines and hydroxyl radical productions release, and severe cerebral ischemia and neuronal damage compared with those of normothermic control rats. However, immediate treatment with the combined agent at the onset of heat stroke confers significant protection against heat stroke-induced circulatory shock, systemic inflammation; cerebral ischemia, cerebral monoamines and hydroxyl radical production overload, and improves neuronal damage and the ST in rats.

Conclusions: Our results suggest that the combination of a colloid substance with a volume-expanding effect and an anti-inflammatory agent may provide a better resuscitation solution for victims with heat stroke.

No MeSH data available.


Related in: MedlinePlus

Histological examination of neuronal damage. The photomicrographs of the cerebral corpus striatum in a normothermic control rat treated with 0.9% NaCl solution (11 ml/kg) (A), a heat stroke rat treated with 0.9% NaCl solution (11 ml/kg) (B), or a heat stroke rat treated with the combined agent (DXM+HES) (C) immediately after the initiation of heat stroke. The striatal photomicrograph in a heat stroke rat treated with DXM (4 mg/kg) is similar to (B), and in a heat stroke rat treated with HES (10%, 11 ml/kg) is similar to (C) (data not shown). Twenty-five minutes after 80-min heat exposure, the corpus striatum of the rat treated with 0.9% NaCl solution showed cell shrinkage, pyknosis of the nucleus, and disappearance of nucleolus. After acute treatment with the combined agent, neuronal damage was reduced, as shown in C. The rats were sacrificed at 25 min after the termination of heat exposure or the equivalent time for the normothermic controls. Scale bar, 50 μm.
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Figure 5: Histological examination of neuronal damage. The photomicrographs of the cerebral corpus striatum in a normothermic control rat treated with 0.9% NaCl solution (11 ml/kg) (A), a heat stroke rat treated with 0.9% NaCl solution (11 ml/kg) (B), or a heat stroke rat treated with the combined agent (DXM+HES) (C) immediately after the initiation of heat stroke. The striatal photomicrograph in a heat stroke rat treated with DXM (4 mg/kg) is similar to (B), and in a heat stroke rat treated with HES (10%, 11 ml/kg) is similar to (C) (data not shown). Twenty-five minutes after 80-min heat exposure, the corpus striatum of the rat treated with 0.9% NaCl solution showed cell shrinkage, pyknosis of the nucleus, and disappearance of nucleolus. After acute treatment with the combined agent, neuronal damage was reduced, as shown in C. The rats were sacrificed at 25 min after the termination of heat exposure or the equivalent time for the normothermic controls. Scale bar, 50 μm.

Mentions: In separate experiments, 25 min after the onset of heat stroke, rats were sacrificed for determination of neuronal damage score in the corpus striatum. The data are summarized in Table 2. After the onset of heat stroke, rats treated with NS (11 ml/kg) displayed higher values of striatal neuronal damage [2 (2, 2.25)] compared with those of normothermic controls [0 (0, 0.75)] (as shown in Table 2 and Figure 5B). Values of striatal neuronal damage score in the DXM-treated rats and in the HES-treated rats were respectively [2 (2, 2)] and [1 (0.25, 1)]. However, with the combined agent [DXM (4 mg/kg)+HES (11 ml/kg)] acute treatment, neuroprotection ensured [1 (0, 1)]. Figure 5 shows that heat stroke-induced cell shrinkage, pyknosis of nucleus, and disappearance of nucleolus in the corpus striatum were attenuated by the combined agent (Figure 5C).


Attenuation of circulatory shock and cerebral ischemia injury in heat stroke by combination treatment with dexamethasone and hydroxyethyl starch.

Yang TH, Shih MF, Wen YS, Ho WY, Leu KL, Wang MY, Liu CC - Exp Transl Stroke Med (2010)

Histological examination of neuronal damage. The photomicrographs of the cerebral corpus striatum in a normothermic control rat treated with 0.9% NaCl solution (11 ml/kg) (A), a heat stroke rat treated with 0.9% NaCl solution (11 ml/kg) (B), or a heat stroke rat treated with the combined agent (DXM+HES) (C) immediately after the initiation of heat stroke. The striatal photomicrograph in a heat stroke rat treated with DXM (4 mg/kg) is similar to (B), and in a heat stroke rat treated with HES (10%, 11 ml/kg) is similar to (C) (data not shown). Twenty-five minutes after 80-min heat exposure, the corpus striatum of the rat treated with 0.9% NaCl solution showed cell shrinkage, pyknosis of the nucleus, and disappearance of nucleolus. After acute treatment with the combined agent, neuronal damage was reduced, as shown in C. The rats were sacrificed at 25 min after the termination of heat exposure or the equivalent time for the normothermic controls. Scale bar, 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2959042&req=5

Figure 5: Histological examination of neuronal damage. The photomicrographs of the cerebral corpus striatum in a normothermic control rat treated with 0.9% NaCl solution (11 ml/kg) (A), a heat stroke rat treated with 0.9% NaCl solution (11 ml/kg) (B), or a heat stroke rat treated with the combined agent (DXM+HES) (C) immediately after the initiation of heat stroke. The striatal photomicrograph in a heat stroke rat treated with DXM (4 mg/kg) is similar to (B), and in a heat stroke rat treated with HES (10%, 11 ml/kg) is similar to (C) (data not shown). Twenty-five minutes after 80-min heat exposure, the corpus striatum of the rat treated with 0.9% NaCl solution showed cell shrinkage, pyknosis of the nucleus, and disappearance of nucleolus. After acute treatment with the combined agent, neuronal damage was reduced, as shown in C. The rats were sacrificed at 25 min after the termination of heat exposure or the equivalent time for the normothermic controls. Scale bar, 50 μm.
Mentions: In separate experiments, 25 min after the onset of heat stroke, rats were sacrificed for determination of neuronal damage score in the corpus striatum. The data are summarized in Table 2. After the onset of heat stroke, rats treated with NS (11 ml/kg) displayed higher values of striatal neuronal damage [2 (2, 2.25)] compared with those of normothermic controls [0 (0, 0.75)] (as shown in Table 2 and Figure 5B). Values of striatal neuronal damage score in the DXM-treated rats and in the HES-treated rats were respectively [2 (2, 2)] and [1 (0.25, 1)]. However, with the combined agent [DXM (4 mg/kg)+HES (11 ml/kg)] acute treatment, neuroprotection ensured [1 (0, 1)]. Figure 5 shows that heat stroke-induced cell shrinkage, pyknosis of nucleus, and disappearance of nucleolus in the corpus striatum were attenuated by the combined agent (Figure 5C).

Bottom Line: Concentrations of the ischemic and damage markers, dopamine, serotonin, and hydroxyl radical productions in corpus striatum, and the serum levels of interleukin-1 beta, tumor necrosis factor-alpha and malondialdehyde (MDA) were observed during heat stroke.After heat stroke, the rats displayed circulatory shock (arterial hypotension), decreased CBF, increased the serum levels of cytokines and MDA, increased cerebral striatal monoamines and hydroxyl radical productions release, and severe cerebral ischemia and neuronal damage compared with those of normothermic control rats.Our results suggest that the combination of a colloid substance with a volume-expanding effect and an anti-inflammatory agent may provide a better resuscitation solution for victims with heat stroke.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department and Institute of Cosmetic Science, Chia-Nan University of Pharmacy and Science, Tainan 71710, Taiwan. ccliu@mail.chna.edu.tw.

ABSTRACT

Background: Increased systemic cytokines and elevated brain levels of monoamines, and hydroxyl radical productions are thought to aggravate the conditions of cerebral ischemia and neuronal damage during heat stroke. Dexamethasone (DXM) is a known immunosuppressive drug used in controlling inflammation, and hydroxyethyl starch (HES) is used as a volume-expanding drug in cerebral ischemia and/or cerebral injury. Acute treatment with a combined therapeutic approach has been repeatedly advocated in cerebral ischemia experiments. The aim of this study is to investigate whether the combined agent (HES and DXM) has beneficial efficacy to improve the survival time (ST) and heat stroke-induced cerebral ischemia and neuronal damage in experimental heat stroke.

Methods: Urethane-anesthetized rats underwent instrumentation for the measurement of colonic temperature, mean arterial pressure (MAP), local striatal cerebral blood flow (CBF), heart rate, and neuronal damage score. The rats were exposed to an ambient temperature (43 degrees centigrade) to induce heat stroke. Concentrations of the ischemic and damage markers, dopamine, serotonin, and hydroxyl radical productions in corpus striatum, and the serum levels of interleukin-1 beta, tumor necrosis factor-alpha and malondialdehyde (MDA) were observed during heat stroke.

Results: After heat stroke, the rats displayed circulatory shock (arterial hypotension), decreased CBF, increased the serum levels of cytokines and MDA, increased cerebral striatal monoamines and hydroxyl radical productions release, and severe cerebral ischemia and neuronal damage compared with those of normothermic control rats. However, immediate treatment with the combined agent at the onset of heat stroke confers significant protection against heat stroke-induced circulatory shock, systemic inflammation; cerebral ischemia, cerebral monoamines and hydroxyl radical production overload, and improves neuronal damage and the ST in rats.

Conclusions: Our results suggest that the combination of a colloid substance with a volume-expanding effect and an anti-inflammatory agent may provide a better resuscitation solution for victims with heat stroke.

No MeSH data available.


Related in: MedlinePlus