Dataset Information

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

ABSTRACT:

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??g/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.

SUBMITTER: Kim SW

PROVIDER: S-EPMC7288434 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Kim Sung Wook SW Oh Joo Suk JS Park Jungtaek J Jeong Hyun Ho HH Oh Young Min YM Choi Semin S Choi Kyoung Ho KH

International journal of emergency medicine 20200610 1

<h4>Background</h4>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.<h4>Methods</h4>This is a prospective, randomized experimental study. Male Sprague-Dawley rats that survived 10 min of four-vessel occlusion were randomly a ...[more]

PMID: 32522270

Similar Datasets

Project description:Cerebral ischemia/reperfusion (I/R) injury causes cognitive deficits, excitotoxicity, neuroinflammation, oxidative stress and brain edema. Vitamin K2 (Menaquinone 4, MK-4) as a potent antioxidant can be a good candidate to ameliorate I/R consequences. This study focused on the neuroprotective effects of MK-4 for cerebral I/R insult in rat's hippocampus. The rat model of cerebral I/R was generated by transient bilateral common carotid artery occlusion for 20 min. Rats were divided into control, I/R, I/R+DMSO (solvent (1% v/v)) and I/R+MK-4 treated (400 mg/kg, i.p.) groups. Twenty-four hours after I/R injury induction, total brain water content, superoxide dismutase (SOD) activity, nitrate/nitrite concentration and neuronal density were evaluated. In addition to quantify the apoptosis processes, TUNEL staining, as well as expression level of Bax and Bcl2, were assessed. To evaluate astrogliosis and induced neurotoxicity by I/R GFAP and GLT-1 mRNA expression level were quantified. Furthermore, pro-inflammatory cytokines including IL-1β, IL-6 and TNF-α were measured. Seven days post I/R, behavioral analysis to quantify cognitive function, as well as Nissl staining for surviving neuronal evaluation, were conducted. The findings indicated that administration of MK-4 following I/R injury improved anxiety-like behavior, short term and spatial learning and memory impairment induced by I/R. Also, MK-4 was able to diminish the increased total brain water content, apoptotic cell density, Bax/ Bcl2 ratio and GFAP mRNA expression following I/R. In addition, the high level of nitrate/nitrite, IL-6, IL-1β and TNF-α induced by I/R was reduced after MK-4 administration. However, MK-4 promotes the level of SOD activity and GLT-1 mRNA expression in I/R rat model. The findings demonstrated that MK-4 can rescue transient global cerebral I/R consequences via its anti-inflammatory and anti-oxidative stress features. MK-4 administration ameliorates neuroinflammation, neurotoxicity and neuronal cell death processes and leads to neuroprotection.

Project description:Neonatal hypoxia-ischemia (nHI) is a major cause of death or subsequent disabilities in infants. Hypoxia-ischemia causes brain lesions, which are induced by a strong reduction in oxygen and nutrient supply. Hypothermia is the only validated beneficial intervention, but not all newborns respond to it and today no pharmacological treatment exists. Among possible therapeutic agents to test, trans-resveratrol is an interesting candidate as it has been reported to exhibit neuroprotective effects in some neurodegenerative diseases. This experimental study aimed to investigate a possible neuroprotection by resveratrol in rat nHI, when administered to the pregnant rat female, at a nutritional dose. Several groups of pregnant female rats were studied in which resveratrol was added to drinking water either during the last week of pregnancy, the first week of lactation, or both. Then, 7-day old pups underwent a hypoxic-ischemic event. Pups were followed longitudinally, using both MRI and behavioral testing. Finally, a last group was studied in which breastfeeding females were supplemented 1 week with resveratrol just after the hypoxic-ischemic event of the pups (to test the curative rather than the preventive effect). To decipher the molecular mechanisms of this neuroprotection, RT-qPCR and Western blots were also performed on pup brain samples. Data clearly indicated that when pregnant and/or breastfeeding females were supplemented with resveratrol, hypoxic-ischemic offspring brain lesions were significantly reduced. Moreover, maternal resveratrol supplementation allowed to reverse sensorimotor and cognitive deficits caused by the insult. The best recoveries were observed when resveratrol was administered during both gestation and lactation (2 weeks before the hypoxic-ischemic event in pups). Furthermore, neuroprotection was also observed in the curative group, but only at the latest stages examined. Our hypothesis is that resveratrol, in addition to the well-known neuroprotective benefits via the sirtuin's pathway (antioxidant properties, inhibition of apoptosis), has an impact on brain metabolism, and more specifically on the astrocyte-neuron lactate shuttle (ANLS) as suggested by RT-qPCR and Western blot data, that contributes to the neuroprotective effects.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets