• Neonatal Medicine
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• v.25 no.1
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• pp.1-6
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• 2018

Extremely low birth weight infants remain at increased risk of intraventricular hemorrhage from the fragile vascular bed of the germinal matrix; the roles of hypotension (ischemia) and reperfusion (hyperemia) in the development of intraventricular hemorrhage are still debated. Cerebrovascular pressure autoregulation protects the brain by maintaining constant cerebral blood flow despite changes in blood pressure. The ontogeny of cerebrovascular pressure autoregulation has not been well established and uncertainty remains about the optimal arterial blood pressure required to support brain perfusion. Another important aspect of premature cerebral hemodynamics is the critical closing pressure--the arterial blood pressure at which cerebral blood flow ceases. Interestingly, in premature infants, the critical closing pressure approximates the mean arterial blood pressure. Often in this unique population, cerebral blood flow occurs only during systole when the diastolic arterial blood pressure is equal to the critical closing pressure. Moreover, the diastolic closing margin, a metric of cerebral perfusion that normalizes diastolic arterial blood pressure to the critical closing pressure, may be a better measure than arterial blood pressure for defining cerebral perfusion in premature infants. Elevated diastolic closing margin has been associated with intraventricular hemorrhage. This review summarizes the current state of understanding of cerebral hemodynamics in premature infants.

• Biomedical Science Letters
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• v.10 no.4
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• pp.467-472
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• 2004

Transcranial Doppler sonography (TCD) is a useful diagnostic method to measure cerebral blood flow velocity in various cerebral disorders. However, we haven't data enough to be available for young persons, especially in the twenties in Korea. This study was performed to collect the basic data of the cerebral blood flow velocity and to understand the cerebral physiology in the twenties. We determined the mean velocities of middle, anterior, and posterior cerebral artery, and vertebral and basilar artery (MCA-V, ACA-V, PCA-V, VA-V, and BA-V, respectively) in eighty-two healthy volunteers. For evaluating cerebral autoregulation, only the MCA- V was measured under various conditions such as stable, apnea, and hyperventilation state. Right and left MCA-V were 80.66±14.03 and 83.22±14.40 cm/sec at stable state, 90.13±17.47 and 90.26±16.38 cm/sec at apnea, and 54.83±11.09 and 55.33±10.74 cm/sec at hyperventilation. Right and left ACA-V were 49.11±15.71 and 48.19±13.75 cm/sec. Right and left PCA-V were 39.44±9.12 and 37.91±6.74 cm/sec. Right and left VA-V were 33.65±9.26 and 36.l8±10.39 cm/sec. BA-V was 48.49±11.16 cm/sec. Right and left MCA- V, V A-V, and right ACA- V and PCA- V in women were higher than those of men (P<0.05). No significant differences were found between men and women in the others. These findings indicate that cerebral hemodynamics and autoregulation were normal in young people in their twenties. The velocities of MCA, ACA, PCA, and BA were high values in women as compared with men.

• Korean Journal of Clinical Laboratory Science
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• v.36 no.1
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• pp.43-48
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• 2004

Cerebral vasoreactivity is an index of autoregulation of cerebral perfusion, and can be measured using functional images such as Xe CT, SPECT and PET in reponse to hypercapneic stimulus. In order to measure cerebral $CO_2$ vasoreactivity in routine TCD study conveniently and reliably, we devised a method of rebreathing into closed volume of reservoir bag as a hypercapneic stimulus, and applied it to 44 healthy volunteers. As a hypercapneic stimulus, we applied fitting mask connected with closed reservoir bag for about 90 seconds, and mean blood flow velocity(MBFV) and pulsatility index(PI) were evaluated at proximal middle cerebral arteries(MCA) of 50-55 mm depth, before and after the hypercapneic stimulus. Age affected the MFV and PI value showed significant and the MFV was 56.45(SD=9.75)cm/sec, while PI was 0.406(SD=0.089). As age increases the flow velocity decreased significantly whereas PI value increased(P<0.05). The vasoreactvity significantly decreased with age(P<0.05). The decrease of cerebral blood flow quantity and cerebral blood flow velocity is not only because of increase of diameter of cerebrovascular resulting from aging, but the resistance increase of small blood vessel resulting from the increase of PI & RI value is regarded. We suppose that the rebreathing method is a reliable and convenient technique as a hypercapneic stimulus in determining cerebral $CO_2$ vasoreactivity. The rebreathing method could be non-invasive and useful methods in estimation of the cerebrovascular reactivity and could be applied to the basal and follow-up evaluation of the cerebrovascular reserve of the ischemic stroke patients.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.287-287
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• 1994

In the present study, it was aimed to asses the possibility that calcitonin gene-related peptide (CGRP) released in response to transient hypotension may contribute to the reflex autoregulation of cerebral blood flow as a putative modulator. Changes in pial arterial diameter (mean, 33.0 ${\pm}$ 1.1 $\mu\textrm{m}$) with changes in systemic arterial blood pressure (mean, 101.9 ${\pm}$ 2.7 mmHg) were observed directly through a closed cranial window in anesthetized normotensive rats. Image of the pial vessels was captured with a stereoscope connected to a CCD video camera and the diameter was measured with a microscaler. In the capsaicin-treated rats (one day prior to experiment, 50 nmol capsaicin injected intracisternally), both vasodilater and vasoconstrictor responses evoked by a transient hypotension and the reverse of blood pressure were markedly attenuated or almost abolished. When changes in pial arterial diameter were plotted as a function of changes in blood pressure, the slopes of both regression lines (for vasodilators and vasoconstrictors ) were markedly reduced. Similar reductions were evidenced under treatment wi th the CGRP antibody serum (1:1,000) and following CGRP receptor desensitization. However, the autoregulatory mechanics were neither affected by treatment wi th spantide (1 ${\mu}$M), substance P antagonist, nor by substance P receptor desensitization. Suffusion wi th mock cerebrospinal fluid containing CGRP and cromakalim caused a vasodilatation in a concentration-dependent manner, respectively and their effects were antagonized by glibenclamide. Substance P produced a vasodilatation, which was, however, little affected by glibenclamide. These observations indicate that the CGRP released from the perivascular sensory fibers in response to a hypotension is implicated in the modulation of the autoregulation of cerebral blood flow.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.5
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• pp.573-580
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• 1998

The study aims to identify the mechanism (s) underlying the altered vasodilatory responses of the pial artery of spontaneously hypertensive rats (SHR) under a hypothesis that calcitonin gene-related peptide (CGRP) exerts a modulator role in the autoregulation of cerebral blood flow (CBF). The animals were divided into four groups: 1) Sprague-Dawley rats (SDR), 2) Wistar rats (WR), 3) SHR with high blood pressure $(BP{\ge}150\;mmHg),$ and 4) SHR with normotensive BP $({\le}150\;mmHg).$ The lower limit of CBF autoregulation in SHR shifted to a higher BP $(82.8{\pm}9.3\'mmHg,\;P<0.05)$ than that in SDR $(58.9{\pm}5.7\;mmHg)$. In SHR, whether the BP levels were high or normotensive, the vasodilator responses to a stepwise hypotension were significantly attenuated unlike with SDR and WR. When artificial cerebrospinal fluid (CSF) containing capsaicin $(3{\times}10^{-7}\;M)$ was suffused over the cortical surface, a transient increase in pial arterial diameter was observed in the SHR with high or normotensive BP. In contrast, SDR and WR showed a large increase in diameter, and the increase was sustained for over 10 minutes. In line with these results, the basal releases of CGRP-like immunoreactivity (CGRP-LI) in the isolated pial arteries from SHR with high and normotensive BP were $12.5{\pm}1.4\;and\;9.8{\pm}2.8\;fmole/mm^2/60\;min\;(P<0.05)$, while those from SDR and WR were $25.5{\pm}3.1\;and\;24.6{\pm}3.1\;fmole/mm^2/60\;min,$ respectively. The isolated basilar arteries showed similar results to those of the pial arteries in SHR. Thus, it is summarized that, in the SHR, the reduced autoregulatory vasodilator responses to stepwise hypotension and capsaicin may be, in part, ascribed to the decreased release of CGRP from the perivascular sensory nerve fibers of the pial arteries, and that altered vasomotor activity in SHR may not be related with the hypertensive tone.

• Journal of Haehwa Medicine
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• v.15 no.2
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• pp.263-272
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• 2006

Purpose Brain vessles have autoregulation function, so even when perfusion pressure drops, cerebral blood flow remain stable by vasodilation. Latest research on this reserve of cerebral vessels is being done using TCD, which measures the reserve of the vessels. We did a research comparing cerebral vessel and peripheral vessel reserve between Taeumin, who are more likely to suffer CVA, and the normal. We observed blood flow of Internal carotid artery siphon and radial indicis artery of the two group with TCD. Method We picked 20 people out of patients diagnosed as cerebral infarction at Cheon-An Oriental hospital of Daejeon University. They were diagnosed as Taeumin with QSCCII questionnaire and constitutional differentiation. Using TCD, we measured highest blood flow rate, mean blood flow and asymmetric counting blood flow of Internal carotid artery siphon and radial indicis artery at rest. And then we measured again after stimulating cerebral vessels, by triggering hypercapnia by self apnea and peripheral vessels by palm heating. Result At rest, mean blood flow rate of Internal carotid artery siphon showed significant decrease compared to control group. Blood flow rate of Internal carotid artery siphon after hypercapnia showed significant decline in highest blood flow rate and mean blood flow compared to control group. Cerebral vessel reaction after the hypercapnia induction showed great change in experiment group than the control group. Peripheral vessel reaction after palm heating showed significant decline in experiment group compared to control group. Conclusion In conclusion, measuring the alteration of blood flow used in diagnosing cerebral infarction, is more sensitive when vessel stimulation is done. Non-invasive TCD is effective especially in case of Taeumin who are more likely to suffer vascular disorder than others.

• Journal of Life Science
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• v.23 no.2
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• pp.157-166
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• 2013

This study aimed to investigate whether nociceptin contributes to the alterations in cerebral blood flow (CBF) regulation following postnatal exposure to ethanol in Sprague-Dawley rats. Animals received ethanol twice a day, 2 hr apart, on postnatal 6, 7 and 8 days. The changes in regional CBF (rCBF) in response to the changes in mean arterial blood pressure were determined at 4-, 8-, and 12-week of age by laser-Doppler flowmetry. Hypotension was induced by the gradual withdrawal of blood from arterial catheter, and the reversal of blood pressure was produced by the reinfusion of blood. Expression of nociceptin-like immunoreactivity was determined in dura mater and cerebral cortex using immunohistochemistry. Postnatal exposure to ethanol almost abolished the autoregulation of rCBF in all age groups. Pretreatment with nociceptin but not with [$Nphe^1$]nociceptin(1-13)$NH_2$, a selective competitive nociceptin receptor antagonist, 5 min prior to ethanol administration preserved the autoregulation of rCBF in all age groups. Postnatal exposure to ethanol markedly increased the expressions of nociceptin-like immunoreactivity in the dura mater and cerebral cortex, both of which were significantly inhibited by pretreatment with 7-nitroindazole monosodium salt as well as aminoguanidine 5 min prior to ethanol administration in all age groups. The values of arterial blood gas analysis were not significantly different from the basal levels in all groups. These results suggest that nociceptin deeply contributes to the compensatory mechanisms for the nitric oxide-dependent alterations in CBF autoregulation following postnatal exposure to ethanol.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.257-263
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• 2009

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1 ${\alpha}$ (HIF-1 ${\alpha}$) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1 ${\alpha}$ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

• Biomedical Science Letters
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• v.11 no.2
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• pp.211-219
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• 2005

Trigeminovascular system plays an important role for the cerebral memodynamics. The aim of this study was to investigate the alterations in cerebrovascular reactivity by trigeminovascular system injury in rats. Trigeminovascular system of male Sprague-Dawley rats was injured by either denervation of nasocilliary nerve or neonatal capsaicin treatment. Trigeminovascular system was stimulated by controlled hemorrhagic hypotension or somatosensory (whisker) stimulation. Changes in regional cerebral blood flow (rCBF) and pial arterial diameter were continuously measured by laser-Doppler flowmetry and videomicroscopy, respectively. Nitric oxide synthase (NOS) activity in cerebral cortex was determined by measuring the conversion of $L-^3H-arginine\;to\;L-^3H-citrulline$. Cyclic GMP levels in cerebral cortex and pial artery were determined using the cyclic GMP $^{125}I$ scintillation proximity assay system. rCBF autoregulation was impaired or almost abolished by trigeminovascular system injury. rCBF response to whisker stimulation was significantly attenuated by trigeminovascular system injury. NOS activity as well as cyclic GMP level in cerebral cortex and pial artery were significantly reduced in the group of trigeminovascular system injury. These results suggest that trigeminovascular system injury causes prominent alterations in cerebrovascular reactivity, and that NO, which is generated by neuronal NOS in the trigeminovascular system, is implicated in the regulation of rCBF.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.27-37
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• 1995

In anesthetized rats, we examined the possibility that endothelium-derived relaxing factor (EDRF) or nitric oxide (NO) released in response to cholinergic mechanism may contribute to the reflex autoregulation of cerebral blood flow. Suffusion with mock cerebrospinal fluid (CSF), containing acetylcholine (ACh, $10^{-9}{\sim}10^{-6}M$) evoked concentration-dependent vasodilatation of the resting pial artery (mean, $19.3{\pm}1.7{\mu}m$, n=36), which was significantly inhibited not only by $N{\omega}$-nitro-L-arginine (L-NNA, $10^{-5}M$) but also by methylene blue ($10^{-6}M$) and oxyhemoglobin ($10^{-6}M$). The muscarinic receptors in the endothelium of pial artery implicated in the release of EDRF were considered to be $M_1\;and\;M_3$ subtypes. When suffused with mock CSF containing L-arginine it caused a transient vasodilatation, which was strongly inhibited by LY 83583 ($10^{-5}M$), but not by L-NNA ($10^{-5}M$). Additionally, both ACh- and L-arginine-induced vasodilation were significantly inhibited by glibenclamide, a specific ATP-sensitive $K^+$ channel blocker. On the other hand, changes in pial arterial diameter were plotted as a function of changes in systemic arterial blood pressure. The slopes of regression lines for vasodilation and vasoconstriction were not affected by pretreatment with $10^{-5}M$ L-NNA, but significantly reduced by $3{\times}10^{-6}M$ glibenclamide. Thus it is suggested that the reflex vasodilation of rat pial arteries in response to a transient hypotension is not mediated by EDRF (NO).