• The Korean Journal of Pain
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• v.13 no.2
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• pp.143-148
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• 2000

Background: Trigeminovascular system is implicated in the pathophysiology of the headache in migraine. This study was designed to evaluate the pattern of Fos protein expression in trigeminal nociceptive central pathway after meningeal stimulation of rats by capsaicin. Methods: The expression of Fos protein was examined by immunohistochemistry in thalamus, brainstem and upper cervical cord (at three levels corresponding to obex, 0.8 mm and 2 mm below obex) 2 hours after intracisternal injection of either diluted capsaicin solution (0.1 ml, $61{\mu}g/ml$) or normal saline (0.1 ml) through a catheter placed in the cisterna magna, or following epidural instillation of diluted capsaicin solution in urethane-anesthetized Sprague-Dawley rats. Results: Fos immunoreactivity was strongly expressed within lamina I, II of bilateral trigeminal nucleus caudalis (TNC) after cisternal capsaicin injection and magnitude of expression was greatest at level 2.0 mm below obex. Epidural capsaicin caused much less labelling than cisternal capsaicin. Fos positive cells were also observed in area postrema, nucleus of the solitary tract, medullary reticular nucleus and midline nuclear groups of the thalamus with similar intensity between capsaicin and control group. Conclusions: These results indicate that the injection of capsaicin into the cisterna magna is an effective stimulus for the induction of Fos protein within TNC through activation of trigeminovascular afferents and this animal model can be useful for the evaluation of the pathophysiology and drug development in migraine and related headache.

• Journal of Korean Neurosurgical Society
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• v.61 no.4
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• pp.434-440
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• 2018

Objective : The purpose of this study was to find an optimal delivery route for clinical trials of intrathecal cell therapy for spinal cord injury in preclinical stage. Methods : We compared in vivo distribution of Cy5.5 fluorescent dye in the spinal cord region at various time points utilizing in vivo optical imaging techniques, which was injected into the lateral ventricle (LV) or cisterna magna (CM) of rats. Results : Although CM locates nearer to the spinal cord than the LV, significantly higher signal of Cy5.5 was detected in the thoracic and lumbar spinal cord region at all time points tested when Cy5.5 was injected into the LV. In the LV injection Cy5.5 signal in the thoracic and lumbar spinal cord was observed within 12 hours after injection, which was maintained until 72 hours after injection. In contrast, Cy5.5 signal was concentrated at the injection site in the CM injection at all time points. Conclusion : These data suggested that the LV might be suitable for preclinical injection route of therapeutics targeting the spinal cord to test their treatment efficacy and biosafety for spinal cord diseases in small animal models.

• Journal of Yeungnam Medical Science
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• v.39 no.1
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• pp.58-61
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• 2022

Mega cisterna magna (MCM), one of the members of the Dandy-Walker complex, is a developmental malformation of the posterior fossa that is larger than 10 mm but morphologically does not affect the vermis and cerebellar hemispheres. Reports of psychiatric disorders associated with this anomaly are rare. We present the case of a patient with MCM who presented with a psychotic manic attack and was diagnosed with bipolar disorder. A 28-year-old female, single housewife, university graduate, presented with irritability, decreased sleep and appetite, distraction, and agitation. The patient also had a delusion of reference. In the clinical follow-up, an increase in energy and an increase in the amount of speech were observed. Her neurological examination was normal, and cranial magnetic resonance imaging revealed an MCM. The relationship and clinical significance of MCM with psychosis and mood disorders have not yet been fully elucidated. It is not known whether this association is accidental or based on etiological commonality. The purpose of this case report is to review the relationship between the cerebellum and psychiatric symptoms and to contribute to the literature.

• Journal of Korean Neurosurgical Society
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• v.59 no.5
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• pp.512-517
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• 2016

Objective : The pathophysiology of idiopathic Chiari malformation (CM) type 1 is disturbance of free cerebrospinal fluid (CSF) flow and restoration of normal CSF flow is the mainstay of treatment. Additional migration of the medulla oblongata in pediatric patients is referred to as CM type 1.5, but its significance in adult patients is unknown. This study is to compare surgical outcomes of adult idiopathic CM type 1.5 with that of type 1. Methods : Thirty-eight consecutive adult patients (M : F=11 : 27; median, 33.5; range, 18-63) with syringomyelia due to idiopathic CM type 1 were reviewed. Migration of the medulla oblongata was noted in 13 patients. The modified McCormick scale (MMS) was used to evaluate functional status before and one year after surgery. All patients underwent foramen magnum decompression and duroplasty. Factors related to radiological success (${\geq}50%$ decrease in the diameter of the syrinx) were investigated. The follow-up period was $72.7{\pm}55.6$ months. Results : Preoperative functional status were MMS I in 11 patients and MMS II in 14 of CM type 1 and MMS I in 8 and II in 5 of CM type 1.5. Of patients with MMS II, 5/14 patients in group A and 3/5 patients in group B showed improvement and there was no case of deterioration. Radiological success was achieved in 32 (84%) patients and restoration of the cisterna magna (p=0.01; OR, 46.5) was the only significant factor. Conclusion : Migration of the medulla oblongata did not make a difference in the surgical outcome when the cisterna magna was restored.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.11a
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• pp.99-113
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• 1996

Taurine, a ${\beta}$-amino acid, plays an important role as a neuromodulator and is necessary for the normal development of the brain. Since de novo synthesis of taurine in the brain is minimal and in vivo studies suggest that taurine does not cross the blood-brain barrier, the blood-cerebrospinal fluid (CSF) barrier is likely to play a role in taurine transport between the central nervous system and the systemic circulation. Therefore, we examined in vivo elimination of taurine from the CSF in the rat to characterize in vivo kinetics of elimination for taurine from the CSF is consistent with the in vitro study. Using a stereotaxic device, cannulaes were placed into the lateral ventricle and the cisterna magna of the rat. Radio-labelled taurine and inulin (a marker of CSF flow) were injected into the lateral ventricle, and the concentrations of the labelled compounds in the CSF were monitored for up to 3 hrs in the cisterna magna. The apparent clearance of taurine from CSF was greater than the estimated CSF flow (p<0.005), indicating that there is a clearance process in addition to the CSF flow. Taurine distribution into the choroid plexus was at least 10 fold higher than that found in other brain areas (e.g., cerebellum, olfactory bulb and cortex). When unlabelled taurine was co-administered with radio-labelled taurine, the apparent clearance of the labeled taurine was reduced (p<0.01), suggesting a saturable disposition of taurine from CSF. Distribution of taurine into the choroid plexus, cerebellum, olfactory bulb and cortex was similarly diminished, indicating that the saturable uptake of taurine into these tissues is responsible for the non-linear disposition. A pharmacokinetic model involving first order elimination and saturable distribution described these data adequately. The Michaelis-Menten rate constant estimated from in vivo elimination study is similar to that obtained in the in vitro uptake experiment Collectively, our results demonstrate that taurine is transported in the choroid plexus via a taurine is cleared from the CSF via a saturable process. This process may be functionally relevant to taurine homeostasis in the brain.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.7-20
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• 1995

Taurine, a ${\beta}-amino$ acid, plays an important role as a neuromodulator and is necessary for the normal development of the brain. Since de novo synthesis of taurine in the brain is minimal and in vivo studies suggest that taurine dose not cross the blood-brain barrier, we examined whether the choroid plexus, the blood-cerebrospinal fluid (CSF) barrier, plays a role in taurine transport in the central nervous system. The uptake of $[^3H]-taurine$ into ATP depleted choroid plexus from rabbit was substantially greater in the presence of an inwardly directed $Na^+$ gradient taurine accumulation was negligible. A transient in side-negative potential gradient enhanced the $Na^+-driven$ uptake of taurine into the tissue slices, suggesting that the transport process is electrogenic, $Na^+-driven$ taurine uptake was saturable with an estimated $V_{max}$ of $111\;{\pm}\;20.2\;nmole/g/15\;min$ and a $K_M\;of\;99.8{\pm}29.9\;{\mu}M$. The estimated coupling ratio of $Na^+$ and taurine was $1.80\;{\pm}\;0.122.$ $Na^+-dependent$ taurine uptake was significantly inhibited by ${\beta}-amino$ acids, but not by ${\alpha}-amino$ acids, indicating that the transporter is selective for ${\beta}-amino$ acids. Since it is known that the physiological concentration of taurine in the CSF is lower than that in the plasma, the active transport system we characterized may face the brush border (i.e., CSF facing) side of the choroid plexus and actively transport taurine out of the CSF. Therefore, we examined in vivo elimination of taurine from the CSF in the rat to determine whether elimination kinetics of taurine from the CSF is consistent with the in vitro study. Using a stereotaxic device, cannulaes were placed into the lateral ventricle and the cisterna magna of the rat. Radio-labelled taurine and inulin (a marker of CSF flow) were injected into the lateral ventricle, and the concentrations of the labelled compounds in the CSF were monitored for upto 3 hrs in the cisterna magna. The apparent clearance of taurine from CSF was greater than the estimated CSF flow (p<0.005) indicating that there is a clearance process in addition to the CSF flow. Taurine distribution into the choroid plexus was at least 10 fold higher than that found in other brain areas (e. g., cerebellum, olfactory bulb and cortex). When unlabelled taurine was co-administered with radio-labelled taurine, the apparent clearance of taurine was reduced (p<0.0l), suggesting a saturable disposition of taurine from CSF. Distribution of taurine into the choroid plexus, cerebellum, olfactory bulb and cortex was similarly diminished, indicating that the saturable uptake of taurine into these tissues is responsible for the non-linear disposition. A pharmacokinetic model involving first order elimination and saturable distribution described these data adequately. The Michaelis-Menten rate constant estimated from in vivo elimination study is similar to that obtained in the in vitro uptake experiment. Collectively, our results demonstrate that taurine is transported in the choroid plexus via a $Na^+-dependent,saturable$ and apparently ${\beta}-amino$ acid selective mechanism. This process may be functionally relevant to taurine homeostasis in the brain.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.15-19
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• 2002

The role of vascular NAD(P)H oxidase in subarachnoid hemorrhage (SAH)-induced vasospasm in the basilar artery was examined in a rat model. Arterial vasospasm characterized by increased wall thickness and decreased lumen size was observed at 5 to 7 days after $2^{nd}$ injection of blood into cisterna magna, and these changes were significantly ameliorated by pretreatment of diphenyleneiodonium $(DPI,\;25\;{\mu}l\;of\;100\;{\mu}M),$ an inhibitor of NAD(P)H oxidase. To determine the time course of changes in the vascular NAD(P)H oxidase activity, cerebral vasculature was isolated at different time intervals from 12 hrs to 14 days after injection of autologous blood. At 24 hrs after the second injection of blood, the NAD(P)H oxidase activity was markedly increased with an enhanced membrane translocation of p47phox, but by 48 hours both the enzyme activity and p47phox translocation regained normal values, and were remained unchanged up to 14 days after SAH. However, no significant changes in the expression of p22phox mRNA was observed throughout the experiments. These findings suggest that the activation of NAD(P)H oxidase by which assembly of the oxidase components enhanced and subsequent production of superoxide in the early stages of SAH might contribute to the delayed cerebral vasospasm in SAH rats.

• Journal of Korean Neurosurgical Society
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• v.29 no.6
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• pp.719-724
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• 2000

Objectives : It has been reported that the presence of a pharmacologically inactive foreign substance, polystyrene latex bead, in subarachnoid space activates a non-specific immunological response and elicits arterial narrowing. Recently the activation of potassium($K^+$) channels may be of benefit in relieving cerebral vasospasm. The present study examined the effects of systemic administration of a ATP-sensitive $K^+$ channel activator, cromakalim, on the polystyrene latex bead-induced cerebral vasospasm. Methods : The spasm models similar to that caused by subarachnoid blood injection were created by injection of bead into rabbit cisterna magna. Intravenous injections of cromakalim were administered twice daily(bid) 30 minutes after induction of vasospasm. Animals were killed by perfusion-fixation 2 days after vasospasm. Basilar arteries were removed and sectioned, and the luminal cross-sectional areas were measured. Results : Injection of bead elicited an arterial constriction, reducing arterial diameter to 33.3% of resting tone. Cromakalim inhibited bead-induced constriction at a dose of 0.3mg/kg(Mann-Whitney test, p<0.01). Conclusion : These results support the concept that the cellular events triggered by inactivation of ATP-sensitive $K^+$ channels are responsible for the pathogenesis of vasospasm. The findings also indicate that cromakalim represents a potential therapeutic agents for the treatment of cerebral vasospasm.

• Clinical and Experimental Pediatrics
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• v.57 no.2
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• pp.75-78
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• 2014

Purpose: This study aimed to investigate the clinical features of macrocephaly at birth in Korea using ultrasonography. Methods: We retrospectively investigated the medical records of full-term birth neonates in Cheil General Hospital & Women's Healthcare Center from January 2000 to June 2012. The following parameters were recorded and analyzed: gestational age, sex, birth weight, height, occipitofrontal circumference (OFC), physical examination, perinatal problems, and ultrasonography results. Macrocephaly was diagnosed when the OFC was greater than two standard deviations, based on the 2007 Korean National Growth Charts. Results: There were 75 neonates with macrocephaly at birth (52 boys and 23 girls), with a mean OFC of $38.1{\pm}0.49cm$. A comparison of the birth weight and height with the OFC value showed that height was correlated with OFC (r=0.35) but birth weight was not correlated with OFC (r=0.06). There were no remarkable findings in 56 cases (75%). Germinal matrix hemorrhage was identified in 10 cases (13%). An enlarged cerebrospinal fluid space was found in 5 cases (6.7%). There were 3 cases of mega-cisterna magna (4%), 1 case of ventriculomegaly, and 1 case of an enlarged interhemispheric space (6 mm) among these patients. In addition, a choroid plexus cyst was seen in 1 case. Mineralizing vasculopathy in both basal ganglia with no evidence of congenital infection was found in 2 cases and an asymptomatic subarachnoid hemorrhage was found in 1 case. Conclusion: Our results indicate that macrocephaly at birth has benign ultrasonography findings and shows a pattern of male dominance.

• Journal of Korean Neurosurgical Society
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• v.58 no.5
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• pp.454-461
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• 2015

Objective : In this study, we aimed to investigate the underlying ethiological factors in chiari malformation (CM) type-I (CMI) via performing volumetric and morphometric length-angle measurements. Methods : A total of 66 individuals [33 patients (20-65 years) with CMI and 33 control subjects] were included in this study. In sagittal MR images, tonsillar herniation length and concurrent anomalies were evaluated. Supratentorial, infratentorial, and total intracranial volumes were measured using Cavalieri method. Various cranial distances and angles were used to evaluate the platybasia and posterior cranial fossa (PCF) development. Results : Tonsillar herniation length was measured $9.09{\pm}3.39mm$ below foramen magnum in CM group. Tonsillar herniation/concurrent syringomyelia, concavity/defect of clivus, herniation of bulbus and fourth ventricle, basilar invagination and craniovertebral junction abnormality rates were 30.3, 27, 18, 2, 3, and 3 percent, respectively. Absence of cisterna magna was encountered in 87.9% of the patients. Total, IT and ST volumes and distance between Chamberlain line and tip of dens axis, Klaus index, clivus length, distance between internal occipital protuberance and opisthion were significantly decreased in patient group. Also in patient group, it was found that Welcher basal angle/Boogard angle increased and tentorial slope angle decreased. Conclusion : Mean cranial volume and length-angle measurement values significantly decreased and there was a congenital abnormality association in nearly 81.5 percent of the CM cases. As a result, it was concluded that CM ethiology can be attributed to multifactorial causes. Moreover, congenital defects can also give rise to this condition.