Correcting for Brain Swelling’s Effects on Infarct Volume Calculation After Middle Cerebral Artery Occlusion in Rats

McBride, Devin W.; Klebe, Damon; Tang, Jiping; Zhang, Junyi

doi:10.1007/s12975-015-0400-3

Cited by 63 publications

(34 citation statements)

References 47 publications

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“…Seven 1-mm thick coronal sections from each brain were stained with 2% TTC solution (2,3,5-triphenyltetrazolium chloride- Sigma-Aldrich, St. Louis, MO) for 2 min and scanned. Infarction and total hemispheric areas were blindly measured using Image J software and corrected for edema based on recent optimizations using the formula: [(infarct V/ipsilateral V) × contralateral V] 47 . Hemispheric edema was calculated as the area difference in the ischemic hemisphere compared to the contralateral hemisphere.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of the NLRP3-inflammasome as a potential approach for neuroprotection after stroke

Ismael

Zhao

Nasoohi

et al. 2018

Sci Rep

201

120

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Activation of the NOD-like receptor protein (NLRP3)-inflammasome has been postulated to mediate inflammatory responses to brain damage during ischemic/reperfusion (I/R) injury. We therefore hypothesized that MCC950, a selective NLRP3-inflammasome inhibitor provides protection in mouse model of transient middle cerebral artery occlusion (tMCAO). Focal cerebral ischemia was induced by 60 min tMCAO followed by intraperitoneal administration of MCC950 (50 mg/kg) or saline at 1 h and 3 h post-occlusion. After 24 h of I/R, mice were tested for neurological outcome and were sacrificed for the analysis of infarct size and estimating NLRP3-inflammasome and apoptotic markers as well. Spectrophotometric method was used to determine hemoglobin (Hb) content as a marker of intracerebral hemorrhage. MCC950-treated mice showed a substantial reduction in infarction, edema and Hb content compared to saline controls in parallel with improved neurological deficits. MCC950 reduced expression of NLRP3-inflammasome cleavage products Caspase-1 and interlukin-1β (IL-1β) in penumbral region. These protective effects of MCC950 were associated with decreased TNF-α levels as well as poly (ADP-ribose) polymerase (PARP) and Caspase-3 cleavage and paralleled less phosphrylated NFκBp65 and IκBα levels. Taken together, these data indicate that inhibition of NLRP3-inflammasome with MCC950 has therapeutic potential in ischemic stroke models. Further investigations into the therapeutic efficacy and protocols are needed to confirm whether MCC950 treatment could be a promising candidate for clinical trials.

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Section: Methodsmentioning

confidence: 99%

Inhibition of the NLRP3-inflammasome as a potential approach for neuroprotection after stroke

Ismael

Zhao

Nasoohi

et al. 2018

Sci Rep

201

120

View full text Add to dashboard Cite

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“…Edema compensation. Edema compensation for TTC-stained coronal slices was computed according to the previously published methods (65,66). First, we measured infarct volume including edema at the photothrombosis induction site (V e ).…”

Section: Behavior Experimentsmentioning

confidence: 99%

Adrenergic receptor antagonism induces neuroprotection and facilitates recovery from acute ischemic stroke

Monai

Wang

Yahagi

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Spontaneous waves of cortical spreading depolarization (CSD) are induced in the setting of acute focal ischemia. CSD is linked to a sharp increase of extracellular K + that induces a long-lasting suppression of neural activity. Furthermore, CSD induces secondary irreversible damage in the ischemic brain, suggesting that K + homeostasis might constitute a therapeutic strategy in ischemic stroke. Here we report that adrenergic receptor (AdR) antagonism accelerates normalization of extracellular K + , resulting in faster recovery of neural activity after photothrombotic stroke. Remarkably, systemic adrenergic blockade before or after stroke facilitated functional motor recovery and reduced infarct volume, paralleling the preservation of the water channel aquaporin-4 in astrocytes. Our observations suggest that AdR blockers promote cerebrospinal fluid exchange and rapid extracellular K + clearance, representing a potent potential intervention for acute stroke.photothrombotic stroke | adrenergic receptor | extracellular potassium ion | aquaporin-4 | AQP4T he ionic composition of the intracellular and extracellular environments in the central nervous system critically influences neuronal networks since action potentials and synaptic input rely on transmembrane electrochemical gradients. Acute stroke disrupts the ion homeostasis in the involving infarct and induces repeated spontaneous waves of cortical spreading depolarization (CSD) in patients (1, 2) and in experimental stroke models (3-5). CSD is initiated as a slowly propagating wave of depolarization that travels across the cortical surface with a velocity of ∼4 mm/min (6). Increases in extracellular potassium (K + ) and glutamate are mediators of CSD (7-10). During the peak of CSD, the extracellular potassium concentration [K + ] e rises from a basal level of 3.5-4.5 to 30-60 mM. This massive rise of [K + ] e depolarizes neurons and astrocytes, resulting in the release of neurotransmitters and the opening of voltage-dependent K + channels and N-methyl-D-aspartate receptors (NMDARs, K + -permeable glutamate receptors), which in a positive feedforward trigger an autoregenerative elevation of [K + ] e as CSD propagates across the cortex (11). The membrane depolarization inactivates voltage-dependent Na + channels, resulting in prolonged electrical silence of neurons. Neurons will gradually regain responsiveness during the recovery period concurrently with normalization of ionic gradients including that of [K + ] e . However, the factors determining [K + ] e recovery are poorly understood, in part because there have been few attempts to monitor cortex-wide network activity linked to CSD following stroke incidents.Astrocytes, a major glial cell type, play a key role in the uptake of K + and the maintenance of ionic homeostasis through Na + -K + pumps (12) and K + channels (13). Additionally, K + uptake is regulated by astrocytic Ca 2+ signaling (14). In experimental animal models, the focal application of high K + on the cortical surface reliably evokes CSD (7). While ...

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“…The infarct volume is the primary outcome for experimental studies on ischemic stroke ( 38 ) and it is the most vigorous index of ischemic brain damage ( 39 ). In the present study, BD treatment for 7 days significantly reduced the infarct volume in the pMCAO rats (P<0.05).…”

Section: Discussionmentioning

confidence: 99%

Protective effects of beef decoction rich in carnosine on cerebral ischemia injury by permanent middle cerebral artery occlusion in rats

Wang

et al. 2017

Exp Ther Med

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Inflammation has a role in the cerebral injury induced by ischemia and the present study aimed to determine the mechanism of the protective effect of beef decoction (BD) with carnosine against it. A rat model of permanent middle cerebral artery occlusion was established using a suture method in the vehicle and each of the BD groups. In experiment 1, 72 Sprague Dawley (SD) rats were randomly divided into three groups: Sham, vehicle and BD-treated group. Rats in the BD group were given 600 mg/kg BD by oral gavage for 1, 3 and 7 days. The sham and vehicle group rats received an equivalent amount of normal saline. In experiment 2, 60 SD rats were randomly divided into six groups: Sham-operated I, sham-operated II, vehicle, low-dose BD, medium-dose BD and high-dose BD group. Rats in the low-, medium- and high-dose BD groups were given BD at the dose of 200, 400 and 600 mg/kg, respectively, by oral gavage for 7 days. Rats in the sham-operated II group were given 600 mg/kg BD. Rats in the sham-operated I group and vehicle group were given the same volume of normal saline by oral gavage. The body weight, neurological deficits and infarct volume were recorded at 1, 3 and 7 days after the operation. Furthermore, the effect of different doses of BD on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) levels in peripheral blood was measured at 7 days. BD-treated rats showed less neurological deficits and a smaller infarct volume at 7 days. BD at 400 and 600 mg/kg significantly decreased the infarct volume in rats. At 600 mg/kg BD, a decline in IL-6, TNF-α, IFN-γ and an increase in IL-4 expression was observed in the BD groups, while no difference in body weight and neurological dysfunction was detected. In conclusion, BD is a neuroprotective agent that may be used as a supplement treatment of ischemic stroke.

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Correcting for Brain Swelling’s Effects on Infarct Volume Calculation After Middle Cerebral Artery Occlusion in Rats

Cited by 63 publications

References 47 publications

Inhibition of the NLRP3-inflammasome as a potential approach for neuroprotection after stroke

Inhibition of the NLRP3-inflammasome as a potential approach for neuroprotection after stroke

Adrenergic receptor antagonism induces neuroprotection and facilitates recovery from acute ischemic stroke

Protective effects of beef decoction rich in carnosine on cerebral ischemia injury by permanent middle cerebral artery occlusion in rats

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