Postoperative change in lateral rectus muscle insertion measured by anterior segment optical coherence tomography.

AimsThe aims of this study were to investigate the longitudinal change in lateral rectus (LR) muscle insertion after recession surgery, and to evaluate a relationship between insertion distance and postoperative amount of deviation.MethodsWe recruited 31 patients who underwent primary LR recession surgery with normal anterior segment structures. An AS-OCT scan of the LR muscle was performed at every visit. Data on sex, age, degree of deviation (prism diopter), and spur-LR insertion distance using AS-OCT were collected at preoperatively and postoperative months 1, 3, and 6. Spur-LR insertion was defined as the shortest distance between the insertion of the LR muscle and the scleral spur was measured using the caliper function in the AS-OCT software.ResultsThe mean distance of spur-LR insertion measured with AS-OCT was 5.5±0.7 mm preoperatively, and 11.1±0.9 mm at 1 month, 11.5±0.8 mm at 3 months, and 11.0±0.7 mm at 6 months postoperatively. There were significant differences in spur-LR insertion between postoperative 1 and 3 months, and between 3 and 6 months (generalized estimating equation, all P<0.001). The overall spur-LR insertion measurement has a significantly negative correlation with postoperative amount of deviation (Pearson's correlation, P=0.035, r=-0.218).ConclusionsAS-OCT is a useful instrument for understanding postoperative changes in EOM after tissue swelling subsides.

Navigation programs, are they helpful for perioperative care with thyroid cancer patients?

The purpose of this study was to develop and evaluate a navigation program for patients with thyroid cancer. The navigation program was developed following an analysis of the unmet needs of patients who underwent surgery for thyroid cancer. Ninety-nine patients in the control group received usual care, and 95 in the navigation group were managed with a navigation program during the perioperative period. The effectiveness of the navigation program was assessed by administering a questionnaire to both groups. Overall satisfaction scores were significantly higher in the navigation than in the control group (p = .025), as were satisfaction scores on the continuity of information (p < .001), the continuity of management (p = .002), the continuity of relationships with healthcare providers (p<.001), and patient empowerment (p < .001). The newly developed navigation program for patients with thyroid cancer was effective in raising satisfaction levels and in actively managing the disease during the perioperative period.

Extraocular muscle injury during endoscopic sinus surgery: an ophthalmologic perspective.

PurposeThe purpose of this study is to describe the clinical characteristics and treatment results of medial rectus muscle (MR) transection incurred during endoscopic sinus surgery.MethodsThis retrospective study included 16 patients with MR transection incurred during endoscopic sinus surgery between 1994 and 2015. The operative notes of the surgical procedure, the pattern of strabismus, the type of muscle injury, the type of corrective strabismus surgery, and the surgical outcomes were reviewed.ResultsNine patients had partial resection of MR and seven patients had complete transection of MR, resulting from an injury incurred during endoscopic sinus surgery. Three of the nine patients with partial resection injury were initially diagnosed as complete resection and subsequently re-diagnosed as partial resection in a review of the images during this study. Five of the nine patients with partial MR resection underwent only simple recession/resection surgery. Patients with complete MR transection underwent muscle transposition or globe fixation surgeries and often multiple operations were required.ConclusionsThe results of this study showed that the treatment strategies could vary depending on the nature of muscle injury. In cases with complete transection, muscle transposition or globe fixation surgeries are often required, with multiple operations. However, partial muscle resection with only simple recession/resection surgery shows a favorable outcome in many cases. The use of proper imaging techniques, a thorough review of the images with various planes, and close follow-up are important for determining the nature of the muscle injury.

Retinal nerve fiber layer thickness in prematurity is correlated with stage of retinopathy of prematurity.

PURPOSE: To compare retinal nerve fiber layer (RNFL) thickness profiles between preterm and full-term children and to investigate factors affecting the RNFL distribution in preterm children. METHODS: We performed Spectral domain optical coherence tomography (SD-OCT) peripapillary RNFL circular scan centered on the optic disc in 50 premature and 58 full-term children. RNFL thickness profiles were compared between preterm and full-term children using a linear regression model. Among preterm patients in this study, 20 patients previously received laser treatment for severe retinopathy of prematurity (ROP). RESULTS: Global average, nasal, and superior disc RNFL thickness profiles were significantly smaller in preterm children (92.70±16.57 µm, 56.02±17.04 µm, and 108.74±27.36 µm, respectively) compared with full-term children (101.63±9.21 µm, P=0.006, 69.14±14.15 µm, P<0.001, and superior, 129.11±18.14 µm, P<0.001, respectively). Multivariable analysis revealed that ROP stage was inversely correlated with nasal RNFL thickness (P=0.010). CONCLUSIONS: Our SD-OCT data demonstrate decreased global average, nasal, and superior disc RNFL thicknesses in preterm children. ROP stage was inversely correlated with nasal RNFL thickness. Further studies are needed to better understand the association between these structural changes and visual functions in preterm children.

Cup-to-disc and arteriole-to-venule ratios in preterm birth.

AIMS: To investigate the influence of preterm birth on the optic disc and retinal vessels by measurements of cup-to-disc (C/D) ratio and arteriole-to-venule (A/V) ratio. METHODS: Eighty-three eyes of 42 preterm births were included. In the age- and sex-matched control group, 83 eyes of 42 full-term births were used. Fundus color photographs were taken. ImageJ software was used to calculate C/D and A/V ratios from the fundus images. RESULTS: Fundus photographs were taken at 8.01 ± 2.22 years of age for the preterm group and 8.01 ± 2.13 years of age for the control group. The mean gestational age of the preterm group was 27(4)/7 weeks (range, 24-34 weeks). The preterm group had significantly larger C/D ratio and smaller A/V ratio (mean ± standard deviation: 0.46 ± 0.12 and 0.59 ± 0.08, respectively) than the control group (0.36 ± 0.07 and 0.68 ± 0.07, respectively) after spherical equivalent refractive error was adjusted. CONCLUSIONS: Preterm birth is significantly associated with larger C/D ratio and smaller A/V ratio. These findings show the effect of preterm birth on the development of optic disc and retinal vessel development.

Assessment of nurses' nutritional knowledge regarding therapeutic diet regimens.

Metabolic diseases and cardiovascular disease (CVD), the incidence of which is currently increasing in Korea, can be managed well with dietary education and modification. However, it has yet to be established whether nurses have sufficient knowledge to impart appropriate nutritional counseling to patients with these diseases. Our study involved 506 nurses working at Asan Medical Center, Samsung Medical Center, and Seoul National University Hospital between March and May, 2006. The questionnaire was comprised of 42 diet-related questions pertaining to diabetes, obesity, and CVD. Nurses' correct-response rate for overall nutritional knowledge was worse than reported in Western countries (58.4%), and particularly so with regard to obesity and CVD. Although many nurses were aware of the therapeutic aspects of nutrients in relation to CVD, most of them had limited knowledge about low-cholesterol diets and sources of water-soluble fiber, fatty acids and the specific food items that prevent CVD. Our results suggest that there is an urgent need to update the contents of nutrition education for nurses to reflect the current changes in the Korean diet and the increasing incidence of metabolic diseases and CVD.

Signaling pathways that mediate nerve growth factor-induced increase in expression and release of calcitonin gene-related peptide from sensory neurons.

Nerve growth factor (NGF) can augment transmitter release in sensory neurons by acutely sensitizing sensory neurons and by increasing the expression of calcitonin gene-related peptide (CGRP) over time. The current study examined the intracellular signaling pathways that mediate these two temporally distinct effects of NGF to augment CGRP release from sensory neurons. Growing sensory neurons in 30 or 100 ng/mL of NGF for 7 days increases CGRP content and this increase augments the amount of CGRP that is released by high extracellular potassium. Overexpressing a dominant negative Ras, Ras(17N) or treatment with a farnesyltransferase inhibitor attenuates the NGF-induced increase in CGRP content. Conversely, overexpressing a constitutively active Ras augments the NGF-induced increase in content of CGRP. Inhibiting mitogen activated protein kinase (MEK) activity also blocks the ability of NGF to increase CGRP expression. In contrast to the ability of chronic NGF to increase peptide content, acute exposure of sensory neurons to 100 ng/mL NGF augments capsaicin-evoked release of CGRP without affecting the content of CGRP. This sensitizing action of NGF is not affected by inhibiting Ras, MEK, or PI3 kinases. In contrast, the NGF-induced increase in capsaicin-evoked release of CGRP is blocked by the protein kinase C (PKC) inhibitor, BIM and the Src family kinases inhibitor, PP2. These data demonstrate that different signaling pathways mediate the alterations in expression of CGRP by chronic NGF and the acute actions of the neurotrophin to augment capsaicin-evoked release of CGRP in the absence of a change in the content of the peptide.

Novel anti-apoptotic mechanism of A20 through targeting ASK1 to suppress TNF-induced JNK activation.

The zinc-finger protein A20 has crucial physiological functions as a dual inhibitor of nuclear factor-κB (NF-κB) activation and apoptosis in tumor necrosis factor (TNF) receptor 1 signaling pathway. Although the molecular basis for the anti-NF-κB function of A20 has been well elucidated, the anti-apoptotic function of A20 is largely unknown. Here, we report a novel mechanism underlying the anti-apoptotic function of A20: A20 blocks TNF-induced apoptosis through suppression of c-jun N-terminal kinase (JNK) by targeting apoptosis signal-regulating kinase1 (ASK1). First, the ectopic expression of A20 drastically inhibits TNF-induced JNK activation and apoptosis in multiple cell types including those deficient of NF-κB activation. Unexpectedly, the blunting effect of A20 on TNF-induced JNK activation is not mediated by affecting the TNFR1 signaling complex formation. Instead, A20 interacts with ASK1, an important MAPKK kinase in the JNK signaling cascade. More importantly, overexpression of wild-type A20, but not of mutant A20 (ZnF4; C624A, C627A), promotes degradation of the ASK1 through the ubiquitin-proteasome system. Taken together, the results from this study reveal a novel anti-apoptotic mechanism of A20 in TNF signaling pathway: A20 binds to ASK1 and mediates ASK1 degradation, leading to suppression of JNK activation and eventually blockage of apoptosis.

Caspase-8 has an essential role in resveratrol-induced apoptosis of rheumatoid fibroblast-like synoviocytes.

OBJECTIVE: Resveratrol is a naturally occurring polyphenol, which possesses chemotherapeutic potential through its ability to trigger apoptosis. The objective of this study was to investigate the major determinant for the apoptotic cell death induction by resveratrol in fibroblast-like synoviocytes (FLS) derived from patients with RA. METHODS: The effect of resveratrol on apoptotic cell death was quantified in a population of subG1 in RA FLS by flow cytometry. The underlying signalling mechanism for apoptotic death was examined by analysing mitochondrial membrane potential, activation of the caspase cascade and translocation of Bid. RESULTS: We show that activation of caspase-8 is essential for triggering resveratrol-induced apoptotic signalling via the involvement of the mitochondrial pathway in RA FLS. Our findings also suggest that this enhanced apoptosis caused by resveratrol occurred in RA FLS irrespective of p53 status. Exposure to resveratrol caused extensive apoptotic cell death, along with a caspase-dependent (activation of caspase-9 and -3, poly ADPribose polymerase (PARP) cleavage and mitochondrial cytochrome c release) or caspase-independent [translocation of apoptosis-inducing factor (AIF) to the nucleus] signalling pathway. Analysis of upstream signalling events affected by resveratrol revealed that the activated caspase-8 triggered mitochondrial apoptotic events by inducing Bid cleavage without any alteration in the levels of Bax, Bcl-xL or Bcl2. The caspase-8 inhibitor or over-expression of crmA abrogated cell death induced by resveratrol and prevented processing of the downstream cascade. CONCLUSION: The results suggest that resveratrol causes activation of caspase-8, which in turn results in modulation of mitochondrial apoptotic machinery to promote apoptosis of RA FLS.

Agmatine reduces infarct area in a mouse model of transient focal cerebral ischemia and protects cultured neurons from ischemia-like injury.

Agmatine is a primary amine formed by the decarboxylation of L-arginine synthesized in mammalian brain. In this study, we investigated the neuroprotective effect of agmatine on ischemic and ischemia-like insults. Primary cortical neuronal cultures were subjected to oxygen-glucose deprivation (OGD), a model of ischemia-like injury, and treated with agmatine before or at the start of OGD, or upon reperfusion. Neuronal death was reduced when agmatine was present during OGD, and this protection was associated with a reduction of nitric oxide (NO) and neuronal nitric oxide synthase (nNOS), but not inducible NOS (iNOS). Protection by agmatine was also studied at the in vivo level using a model of middle cerebral artery occlusion (MCAO) in mice. Mice were subjected to 2 h MCAO. Agmatine was administered either 30 min before ischemia, at the start of MCAO, at the start of reperfusion, or 2 or 5 h into reperfusion. Agmatine markedly reduced infarct area in all treatment groups except when treatment was delayed 5 h. The number of nNOS immunopositive cells was correlated with neuroprotection. Interestingly, immunoreactivity for iNOS was reduced only when agmatine was administered before and at the onset of MCAO. Our study suggests that agmatine may be a novel therapeutic strategy to reduce cerebral ischemic injury, and may act by inhibiting the detrimental effects of nNOS.

Familiarity with, knowledge of, and attitudes toward epilepsy in residents of Seoul, South Korea.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the perceptions of epilepsy in Seoul, South Korea, a country where social stigma toward epilepsy is still pronounced. METHODS: We randomly selected 1000 persons living in Seoul and performed telephone interviews regarding public awareness, knowledge, and attitudes toward epilepsy. RESULTS: Among 1000 respondents, the 92% who had read or heard about epilepsy became the subjects of the study. Word of mouth was most often referenced as a source of knowledge (78%). Forty-seven percentage believed that epilepsy is inheritable, whereas 5% thought that epilepsy is a mental illness. Marriage of their children to an epileptic person, childbearing by women with epilepsy, and employing a person with epilepsy were opposed by more than 50% of respondents. The reasons for the negative attitudes were that epilepsy was hereditary and untreatable (P < 0.05, respectively). CONCLUSIONS: Our study revealed that there still remains negative attitudes regarding the marriage, childbearing, and employment of persons with epilepsy, which may stem from misconceptions about the cause and treatability of epilepsy, possibly due in part to the influence of herbal medicine, and South Korea's ethnic homogeneity. Public health education either through media or school health education is urgently needed to improve knowledge about, and attitudes toward epilepsy.

Dietary supplementation of (+)-catechin protects against UVB-induced skin damage by modulating antioxidant enzyme activities.

PURPOSE: The aim of this study was to investigate the effects of dietary supplementation with (+)-catechin on cutaneous antioxidant enzymes and the skin damage caused by UVB irradiation. METHODS: BALB/c mice were divided into three groups. Each group was fed a regular diet (RD) or a 2% catechin-supplemented diet for either 2 weeks (2CSD) or 4 weeks (4CSD) ad libitum prior to UVB irradiation. Skin was removed for the antioxidant enzyme assay, hematoxylin and eosin staining, and the TEM analysis before and at various time points after UVB (200 mJ/cm2) irradiation. RESULTS: Before UVB irradiation, the superoxide dismutase (SOD) and catalase (CAT) activities of the 2CSD and the 4CSD groups were found to be lower than those of the RD group, whereas the glutathione peroxidase (GPx) activity of the 4CSD group was higher than those of the RD and the 2CSD groups (P<0.05). The SOD and CAT activities of the RD group decreased after UVB irradiation, while those of the 2CSD and the 4CSD groups increased immediately after irradiation and then decreased (P<0.05). Immediately after UVB irradiation, the GPx activities of the 4CSD and the 2CSD groups increased, but that of the RD group decreased. The GPx activity of all three groups showed a tendency to return to pre-UVB irradiation levels with time. Light microscopic findings of the RD group showed epidermal thinning and apoptotic cells at 24 h after UVB irradiation and mostly necrotic cells at 48 h, whereas only moderate thickening of the epidermis was observed in the 2CSD group at 48 h after irradiation. An electron microscopic examination produced similar findings. At 48 h after irradiation, nearly all epidermal cells seemed to be damaged in the RD group as compared to the 2CSD group. CONCLUSION: These results demonstrate that dietary supplementation with (+)-catechin could protect epidermal cells against UVB-induced damage by modulating antioxidant enzyme activities.

Human papilloma virus type 16 E7 genes protect astrocytes against apoptotic and necrotic death induced by hydrogen peroxide.

Hydrogen peroxide is considered to be a dose- and time-dependent mediator in apoptotic and necrotic death. In this study, we examined the signaling of the E6 and E7 proteins with respect to apoptosis or necrosis after H2O2 injury using an in vitro model with overexpressed E6 or E7 genes. For this purpose, the E6 and E7 gene expressing astrocytes were exposed to 10 micromole and 200 micromole H2O2 solutions. Twenty- four hours after treatment with the lower dosage(10 micromole H2O2), control, E6-expressing cells suffered about 45% injury and LXSN-expressing cells decreased by 67% as assessed by LDH release. However, E7-expressing cells showed less injury, resulting in 20-30% of LDH release. Astrocytes expressing E6, E7, LXSN and mock-infected cells showed a typical apoptotic death pattern on the DNA gel after treatment with a low-dose of H2O2 (10 micromole), however they died from necrotic death after a high-dose (200 micromole) H2O2. Overexpression of HPV-E7 genes protected the cells from apoptotic death after a low-dose of H2O2 and from necrotic death after a high-dose of H2O2, while the overexpression of E6 genes from the necrotic death. E7 expressing astrocytes showed higher catalase activity and the levels of E2F protein surged more than 100-folds compared with the control astrocytes. We believe that the activity of E7 protein to protect astrocytes from H2O2 injury was at least partly due to increased catalase, a scavenger protein.

Studies on the changes of c-fos protein in spinal cord and neurotransmitter in dorsal root ganglion of the rat with an experimental peripheral neuropathy.

Animal models for human chronic pain syndromes have been developed and widely used for pain research. One of these neuropathic pain models by Kim and Chung (1992) has many advantages for operation and pain elicitation. In this neuropathic model we have examined the c-fos protein, substance P, CGRP immunoreactivity in dorsal root ganglia and dorsal horn. 50 Sprague-Dawley rats were used for this study. L5 and L6 spinal nerves were ligated tightly to produce the neuropathic pain model. After 2, 4, 8, 16, and 24 hours and 1 week of surgery, rats were anesthetized and sacrificed by perfusion. After confirmation of the roots transected by the surgery, the L5 and L6 dorsal root ganglions and spinal cord were removed and processed for immunohistochemistry. All tissue sections were immunohistochemically stained for substance P, CGRP and c-fos using the peroxidase-antiperoxidase (PAP) method. The number of immunostained substance P and CGRP dorsal root ganglion cells and c-fos immunoreactive dorsal horn cells were counted and analyzed statistically with Mann-Whitney U test. The results are as follows. The number of c-fos protein immunoreactive neurons in the superficial layer of dorsal horn were increased markedly 2 hours after operation, and gradually decreased to normal level 1 week after operation. The number of c-fos protein immunoreactive neurons in the deep layer of the dorsal horn gradually increased to a peak 24 hours after operation, then decreased to the normal level 1 week after operation. The number of substance P and CGRP immunoreactive L5 and L6 dorsal root ganglion neurons were decreased markedly 1 week after the pain model operation. In conclusion, after neuropathic pain model operation, c-fos proteins were immediately expressed in the superficial layer of spinal dorsal horn, thereafter c-fos proteins in the deep layer of spinal dorsal horn were expressed. CGRP and substance P immunoreactive neurons in DRG were decreased markedly 1 week after neuropathic pain model operation. These decrements do not coincide with the other chronic pain models, which show great increases in these pain transmitting substances. Therefore, the relationship between pain and c-fos, SP and CGRP should be investigated further.

Acoustic flowmeter for the measurement of the mean flow velocity in pipes.

This paper proposes a new technique for measuring the gas flow velocity averaged along the finite length of a pipe as well as over its cross-sectional area. Unlike the conventional gas flowmeters, the proposed technique exploits the one-dimensional plane waves that propagate uniformly across the pipe cross-sectional area. When a fluid flows along the pipe, the plane waves are superposed with the flow field such that the positive-going and negative-going plane wave components undergo the change of their wave numbers. Such wave number variation due to the mean flow velocity has provided a major motivation for developing a new way of measuring the mean flow velocity in the pipe, which is referred to as the acoustic flowmeter. To examine the feasibility of the developed flow velocity measurement method, including its theoretical backgrounds, experimental setups are illustrated in this paper. Detailed experimental data for the flow velocity range of 2-27 m/s reveal the linearity of the proposed acoustic flowmeter and its salient environmental robustness for the different acoustic pressure patterns in the pipe and, furthermore, for different velocity profiles over the pipe cross-section area.

Molecular cloning and characterization of a protein tyrosine phosphatase enriched in testis, a putative murine homologue of human PTPMEG.

Protein tyrosine phosphorylation is regulated by protein tyrosine kinase and protein tyrosine phosphatase activities. These two counteracting proteins are implicated in cell growth and transformation. Using polymerase chain reaction with degenerate primers, we have identified a novel mouse protein tyrosine phosphatase (PTP). This cDNA contains a single open reading frame of the predicted 926 amino acids. Those predicted amino acids showed significant identity with human megakaryocyte protein-tyrosine phosphatase by 91% in nucleotide sequences and 94% in amino acid sequences. We have identified that expression of this PTP is highly enriched in the testis in mouse and human and has been termed here as a 'testis-enriched phosphatase' (TEP). Northern analysis detected two mRNA species of 3.7 and 3.2kb for this PTP in mouse testis and the expression of TEP is regulated during development. The recombinant phosphatase domain possesses protein tyrosine phosphatase activity when expressed in Escherichia coli. Immunohistochemical analysis of the cellular localization of TEP on mouse testis sections showed that this PTP is specifically expressed in spermatocytes and spermatids within seminiferous tubules, suggesting an important role in spermatogenesis.

Recent trends and patterns of mortality in Korea.

PIP: Mortality trends and patterns in Korea during 1985-95 were analyzed. The percent change of death rates was calculated from the death registration data, and regression analysis was used to examine the trends of mortality rates. Findings reveal that the declines in infectious, circulatory, and respiratory disease are the primary causes of a reduced mortality rate. The relative decrease of mortality was greater for females than males under age 70 years, although the reverse is observed for those older than 70 years. Among all age groups mortality decrease was the highest among children 5-9 years old. Traffic accidents were the leading cause of death under 40 years of age; liver disease was for those in their 40s. Cerebrovascular diseases were most significant for those aged 50 years and over. Major causes of increased death rates for both sexes included cancer, diabetes, ischemic heart disease, mental and behavioral disorders, traffic accidents, suicide, and homicide. Major causes increasing sex differentials in mortality were tuberculosis, cancer, liver diseases, and mental and behavioral disorders due to psychoactive substance use.^ieng

PAC and cosmid contig spanning the HOXA cluster on human chromosome 7p15.

To construct the PAC and cosmid contig map spanning the HOXA cluster on human chromosome 7, we used 9 DNA markers (D7S2243, D7S3010, HOXA1, EVX1, 750, pBH8, p60, p8.0, and HOXA11), among which the final 4 were generated in this study by shotgun cloning strategy. From the libraries, 5 PAC and 35 cosmid clones were screened and as a result, an overlapping continuous array of cosmid and PAC clones covering the genomic region (about 200 kb) spanning the entire cluster were constructed. The isolated cosmids contained several consecutive HOX genes of regional group, probably sharing the regulatory processes such as alternative splicing or polyadenylation, and thus could be used as useful materials for elucidating the molecular mechanism of HOX gene expression in the future.

Distribution of succinic semialdehyde reductase in rat brain.

Succinic semialdehyde reductase (SSR) that catalyzes the reduction of succinic semialdehyde (SSA) to gamma-hydroxybutyrate (GHB) has been identified as one of the NADPH-dependent aldehyde reductases. Reduction of SSA to GHB strongly supports the proposal that GHB biosynthesis may be an important step in the GABA shunt. It is pharmacologically significant in anesthesia, evoking the state of sleep, and an increase in brain dopamine level. Monoclonal antibodies against bovine brain succinic semialdehyde reductase were produced. Using the anti-succinic semialdehyde reductase antibodies, we investigated the distribution of brain succinic semialdehyde reductase in rat brain. The brain tissues were sectioned with a basis on the rat brain atlas of Paxinos and were stained by the immunoperoxidase staining method using monoclonal antibodies. In the section of the frontal lobe, immunoreactive cells were observed in the lateral septal area, the ventral pallidum, which belongs to the substantia innominata. We could observe immunoreactive cells in the reticular thalamic nucleus, which is closely related with 'sleeping', the basal nuclei of Meynert, which is associated with Alzheimer's disease, and hypothalamic nuclei. Immunoreactive cells were also shown in raphe nuclei or the reticular formation of the midbrain, cerebellum, and inferior olivary nuclei of the medulla oblongata. Succinic semialdehyde reductase-immunoreactive cells were distributed extensively in rat brain, especially immunoreactive cells were strongly observed in the areas associated with the limbic system and reticular formation.