Effects of Isoflurane on Transport across the Blood-Brain Barrier

Z., Oak; Anwar, Mujahid; Sinha, Arabinda K.; Wei, Hwu Meei; Klein, Sanford L.; Weiss, Harvey R.

doi:10.1097/00000542-199203000-00016

Cited by 39 publications

(30 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition to its inhibitory effect on ischemic BBB disruption, which is characterized by a marked extravasation of albumin and other macromolecular tracers, as reported in this study, isoflurane-anesthesia has also been previously reported to decrease the physiological extravasation of an amino acid [40]. Moreover, one study reported that isoflurane-anesthesia increases the extravasation of EBD when the tracer was injected at specific time points corresponding to a particular EEG signal [41].…”

Section: Discussionsupporting

confidence: 52%

Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia

et al. 2017

View full text Add to dashboard Cite

Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8–24 h, whereas the late phase of BBB disruption begins 48–58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in comparison to the inhibitors of the neuronal death signaling cascade; these, in fact, can attenuate the infarct volume measured at 24 h post-ischemia when administered at 6 h in our same stroke model.

show abstract

Section: Discussionsupporting

confidence: 52%

Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Interestingly, a prior rat study demonstrated that the CBF in lateral cortex, posterior cortex, pons, and medulla reduced significantly (2% vs 0% isoflurane) but no significant changes were seen in other regions such as anterior cortex, basal ganglia, cerebellum, et al [31]. The discrepancy of isoflurane dosage effects on CBF between rats and monkeys mostly is due to the species difference of anesthetic effects as reported in other mammals including rats, dogs, pigs, cats, rabbits [11, 27, 32-36].…”

Section: Discussionmentioning

confidence: 99%

Effect of high dose isoflurane on cerebral blood flow in macaque monkeys

Patel

Wang

et al. 2014

Magnetic Resonance Imaging

View full text Add to dashboard Cite

The effect of high dose isoflurane on cerebral blood flow (CBF) was investigated in adult macaque monkeys receiving 1% to 2% isoflurane with the pseudo continuous arterial-spin-labeling (pCASL) MRI technique. High concentration (2%) of isoflurane resulted in significant increase in the mean CBF of the global, cortical, subcortical regions and the regional CBF in all subcortical structures and most cortical structures (such as motor cortex, anterior cingulate cortex, but not media prefrontal cortex). In addition, the changes of regional CBF in the affected regions correlated linearly with increasing isoflurane concentrations. The study demonstrates region specific CBF abnormal increase in adult macaque monkeys under high dose (2%) isoflurane and suggests the brain functionality in corresponding structures may be affected and need to be taken consideration in either human or non-human primate neuroimaging studies.

show abstract

“…The degree of osmotic disruption of the BBB could be affected by various factors, such as the osmolarity of a substance and duration of its intra-arterial infusion, the region of the brain, the anesthetic agents used, the P a CO 2 , the blood pressure, and steroids [2,17,18] . In this study, all animals were treated in the same experimental conditions, and blood pressure and blood gases were similar between the groups.…”

Section: Discussionmentioning

confidence: 99%

Effects of VEGF on the Blood-Brain Barrier Disruption Caused by Hyperosmolarity

Z.¹,

Hunter

Liu

et al. 2008

Pharmacology

View full text Add to dashboard Cite

This study was performed to test whether disruption of the blood-brain barrier (BBB) caused by hyperosmolarity could be related to vascular endothelial growth factor (VEGF), using anti-VEGF antibody and ciclopirox olamine (CPX), an inducer of VEGF. CPX 50 mg/kg or normal saline was given intraperitoneally to male Wistar rats 18 h before BBB disruption. Two craniotomies were made on the ipsilateral cortex (IC-1 and IC-2) where the BBB would be disrupted, and a third hole was made on the contralateral cortex (CC) to expose the cortices. We applied normal saline (to IC-1 and the CC) or anti-VEGF antibody (to IC-2) for 90 min before BBB disruption with intracarotid injection of 25% mannitol. The degree of BBB disruption was determined by measuring the transfer coefficient (K_i) of ¹⁴C-α-aminoisobutyric acid and the volume of ³H-dextran distribution. The protein levels of VEGF were determined with Western blot analysis. In the control animals, hyperosmolar mannitol significantly increased (415%) the K_i in IC-1. The K_i was attenuated with anti-VEGF antibody application (–28%, p < 0.05). Even though the protein levels of VEGF were strongly increased with CPX pretreatment, this upregulation did not alter the hyperosmolar BBB disruption in the saline- or in the antibody-treated cortex. The data on the volume of dextran distribution followed the same pattern as that of the K_i but without a statistically significant difference between IC-1 and IC-2 in either group. Our data demonstrated that hyperosmolar BBB disruption could be attenuated with anti-VEGF antibody. However, upregulation of VEGF with CPX did not alter the degree of hyperosmolar BBB disruption with or without anti-VEGF antibody treatment. This study suggests that the contribution of VEGF in hyperosmolar BBB disruption is limited.

show abstract

Effects of Isoflurane on Transport across the Blood-Brain Barrier

Cited by 39 publications

References 0 publications

Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia

Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia

Effect of high dose isoflurane on cerebral blood flow in macaque monkeys

Effects of VEGF on the Blood-Brain Barrier Disruption Caused by Hyperosmolarity

Contact Info

Product

Resources

About