Neuroprotection in Animal Models of Global Cerebral Ischemia

Cervantes, Miguel; González-Burgos, Ignacio; Letechipía-Vallejo, Graciela; Olvera‐Cortés, María Esther; Moralí, Gabriela

doi:10.5772/32322

Cited by 5 publications

(3 citation statements)

References 284 publications

(300 reference statements)

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“…This study revealed that paricalcitol has neuroprotective properties after global cerebral ischemia. The experimental rat model of global cerebral ischemia does not result in long-lasting focal neurological deficits [21]. Therefore, rats that survive longer than 1 day after four-vessel occlusion recovered well, showing equivalent NFSs between the groups.…”

Section: Discussionmentioning

confidence: 89%

Neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia

Kim

Park

et al. 2020

Int J Emerg Med

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Background: Paricalcitol is known to attenuate ischemic-reperfusion injury of various organs. However, it is not known whether paricalcitol prevents neuronal injury after global cerebral ischemia. The purpose of this study is to investigate the neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia. Methods: This is a prospective, randomized experimental study. Male Sprague-Dawley rats that survived 10 min of four-vessel occlusion were randomly assigned to two treatment groups: one group was treated with paricalcitol 1 μg/kg IP, and the other was given an equivalent volume of normal saline IP. Drugs were administered at 5 min, 1 day, 2 days, and 3 days after ischemia. Neurologic function was assessed at 2 h, 1 day, 2 days, 3 days, and 4 days after ischemia. We tested motor function 3 days after ischemia using the rotarod test. Also, we tested memory function 4 days after ischemia using the passive avoidance test. We assessed neuronal degeneration in the hippocampus of surviving rats 4 days after ischemia. Results: Eight rats were allocated to each group. No significant differences were found between the groups in terms of survival rate, motor coordination, or memory function. The neurological function score 2-h post-ischemia was significantly higher in the paricalcitol group (p = 0.04). Neuronal degeneration was significantly less in the paricalcitol group compared with the control group (p = 0.01). Conclusions: Paricalcitol significantly attenuated neuronal injury in the hippocampus. Although motor coordination, memory function, and survival rate were not significantly improved by paricalcitol treatment in this study, paricalcitol remains a potential neuroprotective drug after global cerebral ischemia.

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Section: Discussionmentioning

confidence: 89%

Neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia

Kim

Park

et al. 2020

Int J Emerg Med

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“…Experimental rat model of global cerebral ischemia does not result in long lasting focal neurological deficits [19]. Therefore, rats surviving longer than one day after four-vessel occlusion recovered well,…”

Section: Discussionmentioning

confidence: 95%

Neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia.

Kim

Park

et al. 2020

Preprint

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Background Paricalcitol has been known to attenuate ischemic-reperfusion injury of various organs. However, it is not known whether paricalcitol prevents neuronal injury after global cerebral ischemia.The purpose of this study is to investigate the neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia.Methods This is a prospective, randomized, experimental study. Male Sprague-Dawley rats survived from 10 min of four-vessel occlusion were randomized to the two treatment groups treated with paricalcitol 1 μg/kg IP and an equivalent volume of normal saline IP, respectively. Drugs were administered at 5 min, 1 day, 2 days, and 3 days after ischemia. Neurologic function score was assessed at 2 h, 1 day, 2 days, 3 days, and 4 days after ischemia. We tested the motor function 3 days after ischemia using the rotarod test. Also, we tested memory function 4 days after ischemia using the passive-avoidance test. We assessed neuronal degeneration in the hippocampus of surviving rats 4 days after ischemia.Results 8 rats were allocated to each group. No significant differences were found in terms of survival rate, motor coordination, or memory function. The neurological function score 2 h post ischemia was significantly high in the paricalcitol group (p = 0.04). Neuronal degeneration was significantly less in the paricalcitol group compared with the control (p = 0.01).Conclusions Paricalcitol significantly attenuated neuronal injury in the hippocampus. Although motor coordination, memory function, and survival rate were not significantly improved, paricalcitol remains a potential neuroprotective drug after global cerebral ischemia. Affiliation

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“…Although the 2VOH model of global brain ischemia cannot exactly model the cardiac myopathy and systemic effects of sudden cardiac death, it is well established in the neuroscience literature . The 2VOH model does incorporate a period of profound hypotension, has a very low animal mortality, and allows for precise control over ischemic and reperfusion times, minimizing experimental variation.…”

Section: Limitationsmentioning

confidence: 99%

Combination Therapy With Insulin‐like Growth Factor‐1 and Hypothermia Synergistically Improves Outcome After Transient Global Brain Ischemia in the Rat

Lagina

Calo

Deogracias

et al. 2013

Academic Emergency Medicine

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Objectives: Hypothermia has a well-established neuroprotective effect and offers a foundation for combination therapy for brain ischemia. The authors evaluated the effect of combination therapy with insulin-like growth factor-1 (IGF-1) and hypothermia on brain structure and function in the setting of global brain ischemia and reperfusion in rats.Methods: Male Sprague-Dawley rats were randomly assigned to groups by a registrar. Animals were subjected to 8 minutes of global brain ischemia using bilateral carotid occlusion and systemic hypotension, followed by 7 days (Stage I dose studies) or 28 days (Stage II outcome studies) of reperfusion. Sham controls were subjected to surgery, but not ischemia. Stage II animals were randomized to no treatment, IGF-1 at the dose determined in Stage I, hypothermia (32°C for 4 hours), or a combination of IGF-1 and hypothermia. Stage II animals underwent 21 days of spatial memory testing. At 7 days (Stage I) or 28 days (Stage II), brains were harvested for counting of CA1 neurons. The primary Stage II outcome was a neurologic outcome index computed as the ratio of viable CA1 neurons per 300-lm field to the number of days to reach success criteria on the memory task.Results: Stage I experiments confirmed the neuroprotective effect of the hypothermia protocol and IGF-1 at a dose of 0.6 U/kg. Stage II studies suggested that early neuroprotection with hypothermia and IGF-1 was not well maintained to 28 days and that combination therapy was more beneficial than either IGF-1 or hypothermia alone. Median and interquartile ranges (IQRs) of viable neurons per 300-lm field were 114 (IQR = 99.5 to 136) for sham, three (IQR = 2 to 4.8) for untreated ischemia, four (IQR = 3 to 70.25) for ischemia treated with IGF-1 alone, 25 (IQR = 3 to 70) for ischemia treated with hypothermia alone, and 78 (IQR 47.3 to 97.5) for ischemia treated with combination therapy. Days to memory success criteria were 13.6 (IQR = 11.5 to 15.5 days) for sham, 23.5 (IQR = 20 to 25.5 days) for untreated ischemia, 17.5 (IQR = 15.5 to 25.5 days) for ischemia treated with IGF-1, 15 (IQR = 14.5 to 21 days) for ischemia treated with hypothermia, and 13.5 (IQR = 12.25 to 18.5 days) for ischemia treated with combination therapy. Neurologic outcome indices were 8.5 (IQR = 7.4 to 9.5) for sham, 0.14 (IQR = 0.08 to 0.2) for untreated ischemia, 0.18 (IQR = 0.17 to 4.6) for ischemia treated with IGF-1, 0.7 (IQR = 0.2 to 4.8) for ischemia treated with hypothermia, and 5.7 (IQR = 3.3 to 6.2) for ischemia treated with combination therapy. Statistically significant differences in neuron counts, days to memory test criteria, and outcome index were found between sham and untreated ischemic animals. Of the three treatment regimens, only combination therapy showed a statistically significant difference from the untreated ischemic group for neuronal salvage (p = 0.02), days to criteria (p = 0.043), and outcome index (p = 0.014).Conclusions: Combination therapy with IGF-1 (0.6 U/kg) and therapeutic hypothermia (32°C for 4 hours) at th...

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Neuroprotection in Animal Models of Global Cerebral Ischemia

Cited by 5 publications

References 284 publications

Neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia

Neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia

Neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia.

Combination Therapy With Insulin‐like Growth Factor‐1 and Hypothermia Synergistically Improves Outcome After Transient Global Brain Ischemia in the Rat

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