Middle Artery Research Articles

Predicting hemorrhagic transformation in patients not submitted to reperfusion therapies

BackgroundWell studied in patients with ischemic stroke after reperfusion therapies (RT), hemorrhagic transformation (HT) is also common in patients not treated with RT and can lead to disability even in initially asymptomatic cases. The best predictors of HT in patients not treated with RT are not well established. Therefore, we aimed to identify predictors of HT in patients not submitted to RT and create a user-friendly predictive score (PROpHET). Material and MethodsPatients admitted to a Comprehensive Stroke Center from 2015 to 2017 were prospectively evaluated and randomly selected to the derivation cohort. A multivariable logistic regression modeling was built to produce a predictive grading score for HT. The external validation was assessed using datasets from 7 Comprehensive Stroke Centers using the area under the receiver operating characteristic curve (AUROC). ResultsIn the derivation group, 448 patients were included in the final analysis. The validation group included 2,683 patients. The score derived from significant predictors of HT in the multivariate logistic regression analysis was male sex (1 point), ASPECTS ≤ 7 (2 points), presence of leukoaraiosis (1 point), hyperdense cerebral middle artery sign (1 point), glycemia at admission ≥180 mg/dL (1 point), cardioembolism (1 point) and lacunar syndrome (-3 points) as a protective factor. The grading score ranges from -3 to 7. A Score ≥3 had 78.2% sensitivity and 75% specificity, and AUROC of 0.82 for all cases of HT. In the validation cohort, our score had an AUROC of 0.83. ConclusionsThe PROpHET is a simple, quick, cost-free, and easy-to-perform tool that allows risk stratification of HT in patients not submitted to RT. A cost-free computerized version of our score is available online with a user-friendly interface.

The blood supply of the inferior nasal concha (turbinate): a cadaveric anatomical study.

The blood supply of the lateral nasal wall acquires a great deal of interest for many reasons especially for the treatment of clinical conditions such as epistaxis that sometimes needs surgical interventions and endoscopic sinus and skull base surgeries that requires a good choice of endonasal flaps including inferior nasal concha (commonly named as inferior turbinate by clinicians) flap to close the dural defects. Successful treatment of epistaxis and closure of such defects depends on detailed anatomical knowledge of lateral nasal wall vasculature and a vital flap with good blood supply, respectively. Because of these we aimed to study the blood supply of inferior turbinate, regarding the sources and courses of the blood vessels. Forty formalin-fixed hemisected cadaveric heads were used at Hacettepe University Anatomy Dissection Laboratory. Anatomical dissection of the inferior nasal concha and the lateral nasal wall was done by dissecting microscope. Coloring dye injection to the arteries was performed. After a detailed examination of the lateral nasal wall; the position of the sphenopalatine foramen (SPF) and the sphenopalatine artery (SPA) were identified. The posterior lateral nasal artery (PLNA) found to give middle and inferior conchal (turbinate) arteries. The average length of the inferior turbinate artery (ITA) was 9.057 ± 1.674mm, the diameter was 1.452 ± 0.172mm, the distance from posterior end of inferior turbinate was 7.879 ± 1.52mm. Anastomosis in the lateral nasal wall between the ITA and the anterior ethmoidal and the lateral nasal (branch of the facial artery) arteries were established. The blood supply of inferior nasal concha is mainly provided by ITA and its anastomotic contributors. Detailed knowledge related to it, before surgical interventions, may reduce intraoperative bleeding and increase endoscopic exposure.

Middle and Distal Common Carotid Artery Stenting: Long-Term Patency Rates and Risk Factors for In-Stent Restenosis

PurposeIn the absence of literature data, we aimed to determine the long-term patency rates of middle/distal common carotid artery (CCA) stenting and to investigate predisposing factors in the development of in-stent restenosis (ISR).Materials and MethodsFifty-one patients (30 males, median age 63.5 years), who underwent stenting with 51 self-expandable stents for significant (≥ 60%) stenosis of the middle/distal CCA, were analyzed retrospectively. Patient (atherosclerotic risk factors, comorbidities, medications), vessel (elongation), lesion (stenosis grade, length, calcification, location), and stent characteristics (material, diameter, length, fracture) were examined. Duplex ultrasonography was used to monitor stent patency. The Mann–Whitney U and Fisher’s exact tests, Kaplan–Meier analyses, and a log-rank test were used statistically.ResultsThe median follow-up time was 35 months (interquartile range, 20–102 months). Significant (≥ 70%) ISR developed in 14 patients (27.5%; stenosis, N = 10; entire CCA occlusion, N = 4). Primary patency rates were 98%, 92%, 83%, 73%, and 61% at 6, 12, 24, 60, and 96 months, respectively. Reintervention was performed in six patients (11.8%) with nonocclusive ISR. Secondary patency rates were 100% at 6 and 12 months and 96% at 24, 60, and 96 months. In-stent restenosis developed more frequently (P < .001) in patients with hyperlipidemia; primary patency rates were also significantly worse (Chi-square, 11.08; degrees of freedom, 1; P < .001) in patients with hyperlipidemia compared to those without.ConclusionStenting of the middle/distal CCA can be performed with acceptable patency rates. If intervention is unequivocally needed, patients with hyperlipidemia will require closer follow-up care.Level of EvidenceLevel 3, Local non-random sample.

A case of bronchiectasis with right middle lobe resection after embolization of bronchial artery, inferior phrenic artery, and internal thoracic artery with severe shunt with middle lobe pulmonary artery

A case of bronchiectasis with right middle lobe resection after embolization of bronchial artery, inferior phrenic artery, and internal thoracic artery with severe shunt with middle lobe pulmonary artery

Hemobilia-a rare complication after laparoscopic cholecystectomy-

BackgroundBiliary bleeding is a condition reported by Sandblom as hemobilia. The most common cause of hemobilia is iatrogenicity. But it has also been reported as a rare complication after laparoscopic cholecystectomy (LC).Case presentationA man in his 60s underwent a LC. He was taking a direct Xa inhibitor for paroxysmal atrial fibrillation (pAf) and had a history of thrombectomy. There was variation in the bifurcation of the hepatic artery and cystic artery. The right hepatic artery branches from the common hepatic artery by itself, and the cystic artery is double. He complained of right upper quadrant pain, nausea, and vomiting on the third postoperative day (3POD). Non-contrast computed tomography (CT) showed that a high absorption area was found to fill the common bile duct. Contrast CT showed no pseudoaneurysm formation. Ultimately, he was diagnosed with postoperative hemobilia. Angiographic examination selective for the cystic artery branching from the middle hepatic artery revealed leakage of the contrast agent and a micro-pseudoaneurysm.ConclusionsWe encountered a case of hemobilia after LC. In this case, it was presumed that in addition to the chronic inflammatory changes of the gallbladder wall, extraordinary bifurcation of the hepatic artery and the cystic arteries and easy bleeding due to resumption of a direct Xa inhibitor synergistically caused a micro-pseudoaneurysm and postoperative hemobilia. It was difficult to identify the cause of hemobilia by contrast CT alone. Angiographic examination was useful for identifying and treating the causative artery and needs to perform aggressively.

Higher doses of Melatonin affect ovarian and middle uterine arteries vascular blood flow and induce oestrus earlier in acyclic ewes.

The present study aimed to evaluate the effect of a single intramuscular injection of melatonin on response of oestrus, rate of conception, ovarian and uterine blood supply during the non-breeding season. Melatonin powder was dissolved in dimethyl sulfoxide (DMSO) and olive oil and injected in two dose of 25mg (MEL-1; n=10) and 50mg (MEL-2; n=10) in May. Ten ewes were served as the control (CON). Results showed that oestrous response was higher in the MEL-2 group than in other groups (p<.01). The time to onset of oestrus in both the MEL-1 and MEL-2 groups was significantly shorter, compared with the CON group (p<.01). Pregnancy rates reached 80% and 90% at 45days of gestation. Doppler indices of the right and left ovarian artery were lower in the melatonin groups than in normal groups (p<.01). Both Doppler indices in uterine arteries were not different among two treatment groups (p>.05), but there was a significant difference when compared with the CON group (p<.01), no difference found between two treatment group in the Doppler velocities of middle uterine arteries (p>.05). In conclusion, the definite changes in the studied parameters showed two novel findings; (a) the increase in melatonin dose results in increasing the blood flow expressed by increased Doppler velocities in fatty tailed ewes, (b) as well as, melatonin can initiate the breeding season regardless of the season earlier by 1-2months in ewes.

Single-Institution Experience with Selective Internal Radiation Therapy (SIRT) for the Treatment of Primary and Secondary Hepatic Tumors.

Purpose: We aim to provide results of the real-world experience of a single center in Lebanon on the use of radioembolization to treat liver-only or liver-dominant tumors. Methods: This retrospective review included patients who were evaluated for radioembolization between January 2015 and June 2017 and who had a lung shunt fraction of 20% or less. Tumor responses were determined using the response evaluation criteria in solid tumors (RECIST).Results: Of the 23 Arab patients with a median age of 64 years (range, 36-87 years), eight had hepatocellular carcinoma, four had cholangiocarcinoma, and 11 had liver-only or liver-dominant metastases from other primary cancers. Most (n=17) had multifocal lesions, and 13 had a history of branched (n=8) or main (n=5) portal vein thrombosis. When appropriate, the gastroduodenal artery and middle hepatic artery were embolized for consolidation of radiotherapy; 18 patients required arterial coil occlusion, two had their cystic artery occluded, and one developed cholecystitis, which was successfully treated with antibiotics and supportive care. Another patient developed a post-radioembolization complication-a peptic ulcer unrelated to arterial reflux of microspheres because both the gastroduodenal and right gastric arteries were occluded. The median time to progression was seven months (range, 3-36 months), and median overall survival from radioembolization was 12 months (range, 3-40 months). Tumor responses included five complete responses, 13 partial responses, one stable disease, and four cases of progressive disease. Conclusion: Performing radioembolization in a non-referral, private center in Lebanon resulted in good patient outcomes with few complications.

Ovarian and uterine arteries blood flow waveform response in the first two cycles following superstimulation in cows

To investigate the ovarian and uterine blood flow responses, hemodynamic, circulating ovarian hormones and nitric oxide (NO) after end of treatment by Folltropin. Holstein Friesian (12) cows previously synchronized with CIDR underwent Doppler ultrasound after administrating of FSH daily for 4days in eight injections started on day 10 of the second ovulation (day -5). Oestradiol (E2), progesterone (P4) and nitric oxide (NOMs) were measured. During the follicular phase, follicle area and antrum area of the second cycle reached maximum value on the day of ovulation compared with that in the first cycle, while during the luteal phase, both showed a pattern of increase and decrease. The luteal area and total coloured area increased till day 10 in the first and second cycle. The first cycle ipsilateral ovarian artery (Ov.A) had higher pulsatility (PI) (p=.001), resistance (RI) (p=.001), peak velocity (PSV) (p=.009) and lower end-diastolic velocity (EDV) (p=.003) compared with the second cycle. The increased ipsilateral Ov.A PSV (p=.009) was accompanied by lower EDV. The first cycle ipsilateral middle uterine artery (MUA) had higher PI (p=.001) and RI (p=.001), with lower PSV (p=.001) and EDV (p=.001). It was concluded that blood flow of ovarian and middle uterine arteries changed after the end of superstimulation as the increased ipsilateral Ov. A and MUA PSVs accompanied by lower EDV and both Doppler indices that reflect the amount of ovarian and uterine blood flow waveform.

Impact of middle hepatic artery reconstruction after living donor liver transplantation using the left lobe.

The aim of this study was to clarify the impact of middle hepatic artery reconstruction on the outcomes of duct-to-duct biliary anastomosis after living donor liver transplantation (LDLT) using the left lobe. Among 258 patients who underwent LDLT using the left lobe, 216 patients who underwent hepatic artery reconstruction and one hepatic duct reconstruction with duct-to-duct interrupted anastomosis were divided into three groups: Group A (n=123), one arterial stump with left hepatic artery reconstruction; Group B (n=32), two arterial stumps with only left hepatic artery reconstruction; and Group C (n=61), two arterial stumps with reconstruction of the left and middle hepatic arteries. The outcomes after LDLT were compared among the three groups. No hepatic artery complications occurred. Group B had a significantly greater incidence of anastomotic biliary stricture than Group C. A multivariate analysis with Cox regression revealed that being in Group B was the only significant independent risk factor for postoperative anastomotic biliary stricture after LDLT. Middle and left hepatic artery reconstruction is safe in LDLT and may prevent biliary stricture caused by dual hepatic artery reconstruction when the graft has left and middle hepatic artery stumps.

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms.

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

Acute Reversible Cerebral Vasoconstriction Syndrome With Low-Dose Dihydroergotamine Possibly Potentiated by Valproic Acid and Erenumab: A Case Report

Dihydroergotamine (DHE), in the setting of polypharmacy, may increase the possibility of reversible cerebral vasoconstriction syndrome (RCVS). A 64-year-old woman with chronic migraine and medication-overuse headache (on amitriptyline, duloxetine, erenumab) was electively admitted for 5 days of intravenous (IV) ketamine (up to 55 mg/h) to treat intractable migraine pain. On the seventh day, upon receiving her forth dose of IV DHE (0.25 mg) and the first of IV valproic acid (VPA) (500 mg) adjunctively, she developed acute bilateral decreased visual acuity, bitemporal visual field deficit, and unsteady gait. Brain magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) showed confluent bilateral T2 hyperintensities with punctate restricted diffusion in the occipital lobes associated with multi-segmental narrowing involving anterior, middle, posterior cerebral, and basilar arteries consistent with RCVS. Verapamil was initiated, whereas DHE, neuroleptics, and serotonergic agents were discontinued. Though she continued to have constant, non-thunderclap migrainous headache, her other neurologic symptoms resolved in 24 h. Concomitant use of VPA and erenumab with DHE may result in RCVS. VPA likely displaces the protein-bound DHE causing a transient surge of free DHE level in the serum. Erenumab may have impaired the protective vasodilatory mechanism, augmenting DHE’s vasoconstrictive effect. This case report highlights the importance and awareness of such a drug-drug interaction with DHE. J Neurol Res. 2020;10(1):20-24 doi: https://doi.org/10.14740/jnr558

Comparison of mastoid obliteration with middle temporal artery flap versus open cavity: a comparative study

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; The objective was to study the outcomes of the canal wall down (CWD) mastoidectomy patients in those with soft canal wall reconstruction by using middle temporal artery (MTA) flap in comparison to those with cavity left open.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; A prospective study of 20 patients undergoing CWD surgery was done with 10 in each group of mastoid obliteration and open cavity. The outcomes were studied at 1, 3, 6 and 12 months post-surgery. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; At the final assessment of 12 months post op, the obliteration group had only 10% patients with grade 1 infection while open cavity group had 40% with grade 2 infection. Obliteration of mastoid cavity and reconstruction of canal wall with soft tissue MTA flap gave excellent control of infection.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; The MTA flap is highly flexible and versatile for otologic reconstruction with an excellent arc of rotation and robust blood supply. It does not have the issues of resorption, dehiscence or fistula formation faced in other obliteration techniques.&lt;/p&gt;

External Approach to Buccal Fat Excision in Facelift: Anatomy and Technique.

Masculinization of the face is a common finding in facelift patients. It is attributed to deflation and decent of the midface-jowls coupled with skin laxity. Fullness is evident lateral to the jowl in a small percentage due to prominent buccal fat pad (BFP). The authors sought to examine the anatomy of the BFP, triangulate the prominent BFP with surgical landmarks, and describe an external approach to excise the BFP during facelift surgery. Eighteen cadaveric dissections were performed. Facelift flap was elevated and the prominent buccal extension of the BFP protruding through the superficial-musculo-aponeurotic-system was identified. Measurements were taken from the BFP to surgical landmarks: zygomatic arch, tragus, and gonial angle. The locations of the facial nerve, parotid duct, and vascular pedicle relative to the BFP were calculated. BFP was 4.1 cm inferior to the zygomatic arch, 7.5 cm anterior the tragus, and 4.5 cm medial the gonial angle. The middle facial artery supplied the BFP on the inferior-lateral quadrant in 61% and inferior-medial quadrant in 39% of specimens . In all specimens, the parotid duct traversed the BFP superiorly, and the buccal branches of the facial nerve traversed the capsule superficially. The buccal extension of the BFP can pseudoherniate in the aging face. Excision may improve lower facial contour. Measurements from facial landmarks may help surgeons identify the buccal extension of the BFP intraoperatively. The surgeon must be careful of the vascular pedicle, parotid duct, and the facial nerve. The external approach safely excises buccal fat during facelift dissection while avoiding intraoral incisions and unnecessary contamination.

Efficacy and safety of guidewireless catheterization with a steerable microcatheter in patients scheduled for yttrium-90 radioembolization: a prospective multicenter trial.

IntroductionA steerable, guidewireless microcatheter is of interest to interventional radiologists because it can improve effectiveness and reduce procedure timing and cost.AimTo assess the feasibility and safety of yttrium 90 radioembolization with a new steerable microcatheter without the need to use a guidewire.Material and methodsA steerable microcatheter (Direxion; Boston Scientific, Natick, MA, USA) was prospectively used for yttrium-90 microsphere delivery in 50 patients (57 applications). The following factors were documented: vessel anatomy; shape and position of the guiding catheter; anticipated catheter position; technical success of catheterization; degree of difficulty in maneuvering; time to reach the target position; and complications.ResultsThe microcatheter target position was in the right hepatic artery (n = 30, 53%), the middle hepatic artery (n = 4, 7%), the left hepatic artery (n = 19, 33%), or in a segmental artery (n = 4, 7%). Vessel catheterization was successful in 53 of 57 hepatic arteries (93%). The mean time to reach the target position was 53.3 ±53.0 s. The mean degree of difficulty in maneuvering the catheter to the target position was 2.3 ±1.3 (easy) on a 6-point scale. The only complication observed was mild vasospasm in 1 patient.ConclusionsThe Direxion steerable microcatheter is characterized by unique steerability, allowing yttrium 90 delivery to be performed safely without use of a guidewire.

Integrated analysis of the proteome and transcriptome in a MCAO mouse model revealed the molecular landscape during stroke progression

Strokes usually results in long-term disability and death, and they occur worldwide. Recently, increased research on both on the physiopathological mechanisms and the transcriptome during stroke progression, have highlighted the relationship between stroke progression and immunity, with a special focus on inflammation. Here, we applied proteome analysis to a middle carotid artery occlusion (MCAO) mouse model at 0 h, 6 h, 12 h and 24 h, in which proteome profiling was performed with 23 samples, and 41 differentially expressed proteins (DEPs) were identified. Bioinformatics studies on our data revealed the importance of the immune response and particularly identified the inflammatory response, cytokine- cytokine receptor interactions, the innate immune response and reactive oxygen species (ROS) during stroke progression. In addition, we compared our data with multiple gene expression omnibus (GEO) datasets with and without a time series, in which similar pathways were identified, and three proteins, C3, Apoa4 and S100a9, were highlighted as markers or drug targets for stroke; these three proteins were significantly upregulated in the MCAO model, both in our proteomic data and in the GEO database.

Partial portal vein arterialization during living-donor liver transplantation: a case report

BackgroundHepatic artery thrombosis can lead to graft loss associated with severe hepatic infarction or bile duct ischemia. When anatomical hepatic artery reconstruction is impossible in liver transplantation or hepato-pancreatic biliary surgery, portal vein arterialization (PVA) is proposed as a salvage technique. Herein, we report our experience with a case that showed favorable clinical outcomes after partial PVA during living-donor liver transplantation (LDLT) because of difficulties in arterial reconstruction.Case presentationA 62-year-old woman with non-B, non-C liver cirrhosis complicated with hepatocellular carcinoma was being prepared for LDLT using an extended left lobe graft. The graft presented with two arteries (left hepatic artery, 2 mm; middle hepatic artery, 2 mm). The first anastomosis was performed using the recipient hepatic artery stumps, but no flow was detected on Doppler control because of thrombus formation. The next attempt was executed using the middle colic artery with a radial artery jump graft and the right gastroepiploic artery, but it led to the same result. Thus, the graft oxygen support by the standard arterial procurement was abandoned, and a shunt was created between the ileocecal artery and the vein to obtain PVA. Arteriography of the superior mesenteric artery showed that the shunt was relatively patent, and the portal vein was apparent. No biliary complication or liver abscess occurred postoperatively, and the patient presented with good liver function and no complications related to portal vein hypertension, nor liver fibrosis 18 months after the LDLT.ConclusionPartial PVA with a shunt created between the ileocecal artery and the vein is useful when arterial reconstruction is difficult during LDLT for preventing graft loss caused by severe hepatic infarction or bile duct ischemia.

Desflurane-based balanced anesthesia in reconstructive carotid artery surgery

The aim of the research was to examine the influence of isoflurane inhalation on the circulatory dynamics, encephalic bloodstream and oxygen balance of the patients’ brain during the carotid endarterectomy. 26 patients were examined. There were detected the parameters of central and systemic circulatory dynamics, the speed of the bloodstream in the middle encephalic artery in M, sector, the results of transcranial cerebral oxymetry. The first stages of the operation, the stage of temporary breakoff of the blood circulation in damaged artery territory were accompanied with moderate lowering of indicators of circulatory dynamics. In the process of reinitiation of the bloodstream the reperfusion of brain declared itself moderately. Isoflurane anesthesia to 1 MAK (minimum alveolar concentration) in combination with phentanyl allows to maintain appropriate pain management, stable circulatory dynamics and well-timed awakening of patients during carotid endarterectomy.

Acute Reversible Cerebral Vasoconstriction Syndrome With Low-Dose Dihydroergotamine Possibly Potentiated by Valproic Acid and Erenumab: A Case Report

Dihydroergotamine (DHE), in the setting of polypharmacy, may increase the possibility of reversible cerebral vasoconstriction syndrome (RCVS). A 64-year-old woman with chronic migraine and medication-overuse headache (on amitriptyline, duloxetine, erenumab) was electively admitted for 5 days of intravenous (IV) ketamine (up to 55 mg/h) to treat intractable migraine pain. On the seventh day, upon receiving her forth dose of IV DHE (0.25 mg) and the first of IV valproic acid (VPA) (500 mg) adjunctively, she developed acute bilateral decreased visual acuity, bitemporal visual field deficit, and unsteady gait. Brain magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) showed confluent bilateral T2 hyperintensities with punctate restricted diffusion in the occipital lobes associated with multi-segmental narrowing involving anterior, middle, posterior cerebral, and basilar arteries consistent with RCVS. Verapamil was initiated, whereas DHE, neuroleptics, and serotonergic agents were discontinued. Though she continued to have constant, non-thunderclap migrainous headache, her other neurologic symptoms resolved in 24 h. Concomitant use of VPA and erenumab with DHE may result in RCVS. VPA likely displaces the protein-bound DHE causing a transient surge of free DHE level in the serum. Erenumab may have impaired the protective vasodilatory mechanism, augmenting DHE’s vasoconstrictive effect. This case report highlights the importance and awareness of such a drug-drug interaction with DHE. J Neurol Res. 2020;10(1):20-24 doi: https://doi.org/10.14740/jnr558

Study of the new 4-phenylpyrrolidinone-2 derivative pharmacokinetics and neuroprotective effect in the ischemic stroke animal model

The development of methods of drug therapy and rehabilitation in different periods of ischemic cerebral lesion is currently an urgent problem. Our study was aimed to investigate the pharmacokinetics and anti-ischemic effect of the new 4-phenylpyrrolidone-2 derivative in rats. To study the drug pharmacokinetics, the Wistar rats were once administered with the substance at a dose of 250 mg/kg, then, the substance distribution in blood and cerebral cortex was evaluated. Elimination half-life value was determined, which was 83.2 min. The substance remained in the brain tissue for 24 hours. To assess the anti-ischemic effect, the stroke was modeled by endovascular middle brain artery transition occlusion, and the drug was administered intravenously for 5 days at two doses, 250 and 125 mg/kg. After that the lesion focus volume was evaluated by MRI, as well as the neurological deficit severity, locomotor and explorative behavior. The studied drug significantly decreased the neurological deficit in model animals compared to control group (1.72 vs 4.4, p &lt; 0.05). According to the MRI data, the effect on the ischemic focus was negligible, while the explorative behavior significantly increased under the influence of the 4-phenylpyrrolidone-2 derivative (hole board test, horizontal activity 12.1 ± 6.8, 22.5 ±10.5, p &lt; 0.05). The data obtained allow us to conclude that the studied substance penetrates the blood-brain barrier (BBB), and accumulates in the brain tissue promoting the neurological deficit correction and increasing the explorative behavior in the ischemic stroke model animals.

Propionic acid abrogates the deleterious effects of cerebral ischemic reperfusion injury through nuclear factor-κb signaling in mice

Background: Cerebral ischemia is caused due to insufficient blood flow to brain cells. This study evaluates the therapeutic effects of propionic acid (PA) on the abnormalities induced during the cerebral ischemic-reperfusion (CIR) injury in mice. Materials and Methods: CIR was induced by complete occlusion of the middle artery of the cerebrum for 15 min and reperfusion for 24 h in the experimental C57BL/6 mice. The analysis of mRNA levels of neuronal nitric oxide synthase (nNOS) was performed by reverse transcriptase polymerase chain reaction (RT-PCR). Inflammatory cytokines such as interleukin-6 (IL-6), IL-1 β, and tumor necrosis factor-alpha were quantitated by enzyme-linked immuno sorbent assay. Apoptosis-related proteins and nuclear factor-κB (NF-κB) were analyzed using Western blot technique. Results: PA demonstrated strong therapeutic effects on controlling the expression of nNOS that was analyzed using RT-PCR. Elevated levels of inflammatory cytokines, caspase-3, caspase-9, and phosphorylated NF-κB during cerebral ischemia were significantly controlled during PA treatment. Conclusion: Our findings demonstrated that PA through oral gavage exhibited healthier effects on the damage caused due to CIR injury.