• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 제4회 추계심포지움
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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.

• Korean Journal of Radiology
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• 제1권1호
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• pp.11-18
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• 2000

Objective: To evaluate the hydrodynamic changes occurring in cerebrospinal fluid (CSF) flow in cervical spinal stenosis using the spatial modulation of magnetization (SPAMM) technique. Materials and Methods: Using the SPAMM technique, 44 patients with cervical spinal stenosis and ten healthy volunteers were investigated. The degree of cervical spinal stenosis was rated as low-, intermediate-, or high-grade. Low-grade stenosis was defined as involving no effacement of the subarachnoid space, intermediate-grade as involving effacement of this space, and high-grade as involving effacement of this space, together with compressive myelopathy. The patterns of SPAMM stripes and CSF velocity were evaluated and compared between each type of spinal stenosis and normal spine. Results: Low-grade stenosis (n = 23) revealed displacement or discontinuity of stripes, while intermediate- (n = 10) and high-grade (n = 11) showed a continuous straight band at the stenotic segment. Among low-grade cases, 12 showed wave separation during the systolic phase. Peak systolic CSF velocity at C4-5 level in these cases was lower than in volunteers (p < .05), but jet-like CSF propulsion was maintained. Among intermediate-grade cases, peak systolic velocity at C1-2 level was lower than in the volunteer group, but the difference was not significant (p > .05). In high-grade stenosis, both diastolic and systolic velocities were significantly lower (p < .05). Conclusion: Various hydrodynamic changes occurring in CSF flow in cervical spinal stenosis were demonstrated by the SPAMM technique, and this may be a useful method for evaluating CSF hydrodynamic change in cervical spinal stenosis.

• Journal of Korean Neurosurgical Society
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• 제58권1호
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• pp.1-8
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• 2015

Treatment of Leptomeningeal carcinomatosis (LMC) from solid cancers has not advanced noticeably since the introduction of intra-cerebrospinal fluid (CSF) chemotherapy in the 1970's. The marginal survival benefit and difficulty of intrathecal chemotherapy injection has hindered its wide spread use. Even after the introduction of intraventricular chemotherapy with Ommaya reservoir, frequent development of CSF flow disturbance, manifested as increased intracranial pressure (ICP), made injected drug to be distributed unevenly and thus, the therapy became ineffective. Systemic chemotherapy for LMC has been limited as effective CSF concentration can hardly be achieved except high dose methotrexate (MTX) intravenous administration. However, the introduction of small molecular weight target inhibitors for primary cancer treatment has changed the old concept of 'blood-brain barrier' as the ultimate barrier to systemically administered drugs. Conventional oral administration achieves an effective concentration at the nanomolar level. Furthermore, many studies report that a combined treatment of target inhibitor and intra-CSF chemotherapy significantly prolongs patient survival. Ventriculolumbar perfusion (VLP) chemotherapy has sought to increase drug delivery to the subarachnoid CSF space even in patients with disturbed CSF flow. Recently authors performed phase 1 and 2 clinical trial of VLP chemotherapy with MTX, and 3/4th of patients with increased ICP got controlled ICP and the survival was prolonged. Further trials are required with newly available drugs for CSF chemotherapy. Additionally, new LMC biologic/pharmacodynamic markers for early diagnosis and monitoring of the treatment response are to be identified with the help of advanced molecular biology techniques.

• 대한의용생체공학회:의공학회지
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• 제26권4호
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• pp.193-197
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• 2005

Shunt valves used to treat patients with hydrocephalus were tested to investigate influence of intracranial pressure pulsation on their flow control characteristics. Five commercial shunt valves were tested in the flow loop that simulates pulsed flow under pressure pulsation. As 20cc/hr of flow rate was adjusted at a constant pressure, application of $40mmH_2O$ of pressure pulse increased the flow rate by $67.9\%.$ As a 90cm length catheter was connected to the valve outlet, increase in the flow rate was substantially reduced to $17.5\%.$ As the flow rate was adjusted to 40cc/hr at a constant pressure, increase in the flow rate was $51.1\%$ with the same pressure pulsation of $40mmH_2O$. The results indicated that pressure-flow control characteristics of shunt valves implanted above human brain ventricle is quite different from those obtained by syringe pump test at constant pressures right after manufacture. The influence of pressure pulsation was observed to be more significant at low flow rate and the flexibility of the outlet silicone catheter was estimated to significantly reduce flow increase due to pressure pulsation.

• 대한의용생체공학회:의공학회지
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• 제23권5호
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• pp.391-395
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• 2002

수두증 환자를 치료하기 위해 머리에 시술 되는 션트밸브가 받는 뇌압 펄스가 밸브의 유량조절 특성에 미치는 영향을 수치적으로 해석하였다. 션트밸브를 통한 유량을 계산하기 위하여 밸브 다이아프램이 형성하는 유량 오리피스를 모델링 하여 맥동압력과 변동하는 압력에 의한 다이아프램의 움직임을 고려하였다. 연구 결과, 압력 펄스와 이에 따른 다이아프램의 움직임에 의하여 유량이 40% 이상 증가함을 보였다. 이 결과는, 뇌실에 시술 되는 션트밸브의 압력-유량 조절특성이 제조 직후 맥동이 없는 유량을 공급하는 시린지 펌프를 사용하여 구한 실험 결과와 상당히 다르다는 사실을 보여주었다.

• 한국임상수의학회지
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• 제23권3호
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• pp.366-370
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• 2006

Arachnoid cysts are intra-arachnoid collections of cerebrospinal fluid. They may cause neurological deficit through expansion that can compress normal neural tissue and obstruct cerebrospinal fluid flow. Intracranial arachnoid cysts were found in 4 patients aged 10 months to 20 months(mean age 15 months). The presenting symptoms included circling(dog 2,3), seizure(dog 1), progressive weakness(dog 1,2,3), increasing scoliosis(dog 3), worsening spasticity(dog 3), and salivation(dog 3). One patient showed no symptoms from the intracranial arachnoid cyst. There were no significant findings in complete blood count and serum chemistry. Computed tomography(CT) with/without magnetic resonance imaging(MRI) scans were performed in these cases. Hypodense intracranial arachnoid cyst was observed on CT images in dog 4. Sagittal T1-weighted(T1W) and T2-weighted(T2W) images and transverse T1W and T2W images revealed a intracranial arachnoid cysts with syringohydromyelia(dog 3) and hydrocephalus(dog 3,4) in the brain. Clinical signs of three cases were improved by medication.

• The Korean Journal of Pain
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• 제26권4호
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• pp.336-346
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• 2013

Intrathecal drug delivery is an effective and safe option for the treatment of chronic pathology refractory to conventional pain therapies. Typical intrathecal administered drugs are opioids, baclofen, local anesthetics and adjuvant medications. Although knowledge about mechanisms of action of intrathecal drugs are every day more clear many doubt remain respect the correct location of intrathecal catheter in order to achieve the best therapeutic result. We analyze the factors that can affect drug distribution within the cerebrospinal fluid. Three categories of variables were identified: drug features, cerebrospinal fluid (CSF) dynamics and patients features. First category includes physicochemical properties and pharmacological features of intrathecal administered drugs with special attention to drug lipophilicity. In the second category, the variables in CSF flow, are considered that can modify the drug distribution within the CSF with special attention to the new theories of liquoral circulation. Last category try to explain inter-individual difference in baclofen response with difference that are specific for each patients such as the anatomical area to treat, patient posture or reaction to inflammatory stimulus. We conclude that a comprehensive evaluation of the patients, including imaging techniques to study the anatomy and physiology of intrathecal environment and CSF dynamics, could become essential in the future to the purpose of optimize the clinical outcome of intrathecal therapy.

• Investigative Magnetic Resonance Imaging
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• 제17권2호
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• pp.123-132
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• 2013

목적 : 정상인 경수에 대한 내부 부위별, 경수 레벨별 확산텐서영상과 뇌척수액 속도에 대한 정상인 기준을 마련하고자 하였다. 대상 및 방법 : 정상인을 대상으로 3T MRI를 이용하여 영상을 획득하였다. 확산텐서영상은 척수 레벨별로 각각 미리 정의해둔 백질의 후삭, 좌, 우 측삭과 회백질에 관심영역을 정하여 FA, MD에 대한 평균값을 구하였다. PC 기법을 이용한 뇌척수액 속도 측정은 C2-3, C4-5, C5-6 척수레벨을 각각 스캔한 후, 척수 레벨별 최대 수축기 및 이완기 속도를 측정하였다. 결과 : FA 값과 MD 값에서 회백질과 백질의 내부 구조 사이에서는 통계적으로 유의한 차이 (p < 0.05)를 보였다. 경수 레벨별에서는 회백질의 FA 값에서 통계적으로 유의한 차이(p < 0.05)를 보였으며, 나머지 부분에서는 통계적으로 유의한 차이를 보이지 않았다 (p > 0.05). 뇌척수액 속도 측정 결과, 평균 최대 수축기 속도 $5.18{\pm}2.00cm/sec$, 평균 최대 이완기 속도 $-7.32{\pm}3.18cm/sec$ 이었으며, 경수 레벨별로는 통계적으로 유의한 차이를 보이지 않았다 (p > 0.05). 결론 : 정상인에 대한 경수 확산텐서영상의 정량적 수치 및 경수 레벨에 영향을 받지 않는 뇌척수액 속도에 대한 평균치를 알 수가 있었다.

• Journal of Pharmaceutical Investigation
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• 제25권3호spc1호
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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.

• Journal of Korean Neurosurgical Society
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• 제45권5호
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• pp.315-317
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• 2009

While syringomyelia is not a rare spinal disorder, syringomyelia associated with a spinal arachnoid cyst is very unusual. Here, we report a 62-year-old man who suffered from gait disturbance and numbness of bilateral lower extremities. Spinal magnetic resonance imaging (MRI) showed the presence of a spinal arachnoid cyst between the 7th cervical and 3rd thoracic vertebral segment and syringomyelia extending between the 6th cervical and 1st thoracic vertebral segment. The cyst had compressed the spinal cord anteriorly. Syringomyelia usually results from lesions that partially obstruct cerebrospinal fluid flow. Therefore, we concluded that the spinal arachnoid cyst was causing the syringomyelia. After simple excision of the arachnoid cyst, the symptoms were relieved. A follow-up MRI demonstrated that the syringomyelia had significantly decreased in size after removal of the arachnoid cyst. This report presents an unusual case of gait disturbance caused by syringomyelia associated with a spinal arachnoid cyst.