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Original Articles
- Anterior Neck Approach for 4-vessel Occlusion in Rats: A Study for Immunohistological Changes and the Effects of Aminoguanidine on Neuronal Cell Death in the Hippocampus.
- Young Jun Ahn, Ki Young Choi, Gu Kang, Yong Seok Kim, Seungkoo Lee, Il Young Cheong, Keun Woo Kim
- Korean J Pathol. 2007;41(6):393-405.
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Abstract
PDF - BACKGROUND
Clinically relevant cerebral ischemia is encountered most frequently as a cardiac arrest or as single or multiple occlusions of the intracranial or extracranial cerebral arteries. Yamaguchi et al. has introduced a one-stage anterior approach to occlude the common carotid arteries (CCAs) and vertebral arteries (VAs).
METHODS
We used a 2-stage anterior approach for producing transient global ischemia by 4-vessel occlusion (4-VO). Four to five days after electrocauterization of two VAs using the anterior neck approach, two CCAs were clipped for 10 min under anesthesia. Aminoguanidine (100 mg/kg) was administered intraperitoneally immediately after 4-VO, and then twice a day for three consecutive days. Cresyl violet staining and immunohistochemical analysis for the expression of GFAP, CD11b, nitrotyrosine, iNOS, and Bax were performed, using brain slices obtained from the rats that were sacrificed 1, 3, 5 and 7 days after reperfusion.
RESULTS
Aminoguanidine reduced neuronal cell death in the CA1 region of the hippocampus. Expression of GFAP, CD11b, nitrotyrosine, iNOS, and Bax were significantly increased in the CA1 region of the hippocampus three days after 4-VO.
CONCLUSIONS
We believe that modified 4-VO is a good method to study transient forebrain ischemia as it is simple and inexpensive to perform and can be utilized without stereotaxis, a pivoting dissection microscope, EEG, a laser flowmeter or the use of Mongolian gerbils.
- Correlation Between Neuronal Apoptosis and Expression of Inducible Nitric Oxide Synthase after Transient Focal Cerebral Ischemia.
- Byoung Yuk Yi, Sung Kyoo Hwang, Ku Seong Kang, Hong Hua Quan, Young Mi Lee, Jung Wan Kim, Eun Kyoung Kwak, Ji Young Park, Yoon Kyung Sohn
- Korean J Pathol. 2004;38(6):364-371.
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Abstract
PDF
- BACKGROUND
Neuronal death in acute-phase cerebral ischemic injury is caused by necrosis. However, neuronal injury after reperfusion can be associated with apoptosis.
METHODS
We used Sprague-Dawley rats whose brains were reperfused after middle cerebral artery occlusion for either 30 min or 2 h. We examined a relationship between apoptosis and the expression of inducible nitric oxide synthase (iNOS) in the brain tissue from 3 h to 14 days after reperfusion in both groups.
RESULTS
TUNEL and iNOS positivity were closely related in both groups. The 2-h ischemia group exhibited increases in the amount of TUNEL and iNOS-positive cells for up to 3 days after reperfusion, at which the TUNEL and iNOS-positive cells decreased. The 30-min ischemia group exhibited peak positivity 24 h after reperfusion, followed by a similar decrease. iNOS mRNA expression peaked 3 h after reperfusion in the 30-min ischemia group, at which time it decreased. In the 2-h ischemia group, iNOS mRNA increased 3 h after reperfusion, peaked 24 h after reperfusion, and then decreased.
CONCLUSION
These results indicated the occurrence of delayed apoptosis in transient cerebral ischemia. Increased expression of iNOS is closely associated with this apoptosis, and oxygen free radical-producing materials, such as nitric oxide, may play an important role in the induction of this apoptosis.
- The Effect of Ischemic Preconditioning in Rat Liver: The Expression of Interleukin-1 and Nuclear Factor-B.
- Kum Yoon Seup, Soo Kyoung Lee, Sun zoo Kim, Eun Kyoung Kwak, Ji Young Park, Tae In Park, Han Ik Bae, Yoon Kyung Sohn, In Soo Suh
- Korean J Pathol. 2002;36(4):238-242.
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Abstract
PDF
- BACKGROUND
A short period of ischemia and reperfusion, called ischemic preconditioning, protects various tissues against subsequent sustained ischemic insult. Apoptosis of hepatocytes and sinusoidal endothelial cells are a critical mechanisms of injury in the ischemic liver. Because nuclear factor-B (NF-B) has a significant role in the cell survival, we hypothesized that ischemic preconditioning protects by inhibition of apoptosis through the expression of NF-B, induced by interleukin-1 (IL-1), which is known for enhancement of its transcription and activation.
METHODS
We induced ischemia and reperfusion on rat liver, and performed in situ terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labelling assay and polymerase chain reaction for IL-1 mRNA and NF-B mRNA.
RESULTS
Apoptosis of hepatocytes and sinusoidal endothelial cells, assessed by in situ TUNEL assay, was significantly reduced with preconditioning. The expression of IL-1 mRNA and NF-B mRNA are seen on discrete monoclonal bands around 344 and 356 base pairs, in comparison with normal rat liver, but, there was no significant difference between the ischemia-reperfusion group and the preconditioning group.
CONCLUSIONS
We suggest that ischemic preconditioning confers dramatic protection against prolonged ischemia via inhibition of apotosis through the expression of IL-1 inducing NF-B and its activation. However, we need further study in the activity of NF-B, such as nucleotide shift assay, because the activity of NF-B is regulated by binding of the inhibitory protein, IB.
- Nicotinamide Reduces the Infarct Volume in a Rat Model of Transient Middle Cerebral Artery Occlusion.
- Min Sup Lee, Young Jun Ahn, Ki Young Choi, Gu Kang, Seong Sik Kang, Il Young Cheong, Kun Jai Lee, Keun Woo Kim
- Korean J Pathol. 2006;40(2):93-102.
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Abstract
PDF
- BACKGROUND
Cerebral ischemia depletes ATP and causes irreversible tissue injury. Nicotinamide is a precursor of NAD+ and it is also a poly (ADP-ribose) polymerase (PARP) inhibitor that increases the neuronal ATP concentration and so protects against stroke. Therefore we examined whether nicotinamide could protect against cerebral ischemia by using a model of transient middle cerebral artery occlusion (MCAO) (reperfusion 2 h post ischemia) in Sprague-Dawley rats.
METHODS
Nicotinamide (500 mg/kg) or normal saline was administered intraperitoneally 24 and 0 h before and after MCAO, respectively. The infarction volumes were determined with triphenyltetrazolium chloride staining 24 h after reperfusion. The nitrotyrosine, PAR polymer and PARP-1 expressions were examined by immunohistochemistry with using brain slices obtained from the rats that were sacrificed at 0, 15, 30, 60 and 120 min after reperfusion.
RESULTS
The infarction volumes were significantly attenuated (21.8%, p<0.05). The nitrotyrosine expressions were increased at 0, 15 and 30 min, and those expressions for PARP polymer and PARP-1 were increased at 60 and 120 min, respectively. Nicotinamide partly reduced the expressions for nitrotyrosine and PAR polymer except for PARP-1.
CONCLUSIONS
These results suggest that nicotinamide may attenuate ischemic brain injury through its antioxidant activity and the inhibition of PARP-1.
- Distribution of Free Radicals in Reperfusion Injury after Transient Brain Ischemia.
- Eunkyoung Kwak, Hyungho Suh, Jiyoung Park, Yunsup Kum, Taein Park, Jungwan Kim, Yoonkyung Sohn
- Korean J Pathol. 2000;34(11):893-900.
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Abstract
PDF
- Free radicals are known as an important factor which may act on reperfusion injury after transient or permanent brain ischemia. Numerous studies about cytotoxic function of free radical have been done. Most of these studies demonstrate the function of free radical in reperfusion injury by using radical scavenger or antioxidant as inhibitor of radicals. We used a modification of Karnovsky's Mn2 /diaminobenzidine (DAB) technique to demonstrate intravascular free radicals following transient occlusion and reperfusion of one middle cerebral artery in Sprague-Dawley rats. The MCA was occluded for 2 hours using an intraluminal suture method. The reperfusion time after transient ischemia was 1 hour, 6 hours, and 24 hours, respectively. Animals were perfused transcardially with solution containing Mn2 and DAB. After DAB perfusion, the brains were removed promptly, sectioned in frozen, and stained with methylene blue for light microscopic examination. Upon light microscopic examination, free radicals were confined within intravascular lumen and the amount of deposits increased according to the duration of reperfusion. Upon electron microscopic examination, free radicals were located in nuclear membrane and membrane of mitochondria and RER, and demonstrated as electron dense deposits. In addition, cell processes of the neuron revealed an electron dense deposits beneath the inner side of the membrane. In conclusion, free radicals demonstrated in the reperfusion injury area indicate that free radical acts as an important cytotoxic factor. Intracellular localization of free radicals may explain the relationship between free radical and delayed neuronal injury.
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