Subcellular distribution of persistent sodium conductance in cortical pyramidal neurons.

Cortical pyramidal neurons possess a persistent Na+ current (INaP) which, in contrast to the larger transient current, does not undergo rapid inactivation. Although relatively quite small, INaP is active at subthreshold voltages and therefore plays an important role in neuronal input-output processing. The subcellular distribution of channels responsible for INaP and the mechanisms which render them persistent are not known. Using high-speed fluorescence Na+ imaging and whole-cell recordings in brain slices obtained from mice of either sex, we reconstructed the INaP elicited by slow voltage ramps in soma and processes of cortical pyramidal neurons. We found that in all neuronal compartments, the relationship between persistent Na+ conductance and membrane voltage has the shape of a Boltzmann function. Although the density of channels underlying INaP was about twofold lower in the axon initial segment (AIS) than in the soma, the axonal channels were activated by about 10 mV less depolarization than were somatic channels. This difference in voltage dependence explains why, at functionally critical subthreshold voltages, most INaP originates in the AIS. Finally, we show that endogenous polyamines constrain INaP availability in both somato-dendritic and axonal compartments of non-dialyzed cortical neurons.SIGNIFICANCE STATEMENT:The most salient characteristic of neuronal sodium channels is fast inactivation. However, a fraction of the sodium current does not inactivate. In cortical neurons, persistent current (INaP) plays a prominent role in many important functions. Its subcellular distribution and generation mechanisms are, however, elusive. Using high-speed fluorescence Na+ imaging and electrical recordings, we reconstructed the INaP in soma and processes of cortical pyramidal neurons. We found that at near-threshold voltages INaP originates predominately from the axon, due to the distinctive voltage dependence of the underlying channels and not because of their high density. Finally, we show that the presence of endogenous polyamines significantly constrains INaP availability in all compartments of non-dialyzed cortical neurons.

An Alternative Model of Laser-Induced Stroke in the Motor Cortex of Rats.

BACKGROUND: A common experimental rodent model for stroke includes induction by a technique in which middle cerebral artery is transiently (MCAO-t) or permanently (MCAO-p) occluded by catheterization. However, this model has prominent disadvantages which consist of the high variability of localization and size of the ischemic area, cases of intracranial hemorrhage and high mortality. Furthermore, the duration of a single MCAO operation takes about thirty minutes and requires highly trained staff. In this article, we propose an alternative method, which is based on laser-induced stroke in the motor cortex. In our research, we compared the original MCAO-p and MCAO-t models and a novel laser model. RESULTS: Compared with the impact of original MCAO-p and MCAO-t technique on brain tissue, the minimally invasive laser model demonstrated a decrease in: variability in body temperature, percent of infarcted volume, blood brain barrier breakdown and brain edema, as well as a prominent decrease of mortality and intracranial hemorrhage. Among other findings of this article, it can be noted that damage to the brain tissue in laser groups occurred only in the region of the motor cortex, without involving the striatal area. CONCLUSIONS: The data presented in this paper show that the model of laser irradiation can serve as an effective method of inducible brain cortical infarction and may lead to a better understanding of the pathophysiology of ischemic stroke and the future development of new drugs and other neuro-protective agents.

A multidisciplinary approach for the treatment of young patients with suprasellar osteochondroma.

BACKGROUND: Osteochondroma is the most common benign bone tumor; intracranial osteochondroma is a very rare finding in the neurosurgical literature and most of them arise from the skull base. CASE REPORT: We report a case of suprasellar ostheocondroma in a 16-year-old female, with its CT and MRI appearances, which caused visual deficits, resolved after surgery. DISCUSSION: To our knowledge, this is the fifth case of osteochondroma affecting the suprasellar region that has been reported, with all the characteristic features of this tumor: optic chiasmal syndrome, intralesional calcifications, cartilage cap, and contrast enhancement. CONCLUSION: Multidiscplinary teams, including a neuro-ophthalmologist, endocrinologist, neuroradiologist, neurosurgeon, and neuropathologist are needed for correct treatment of the disease and appropriate follow-up.

Early Surgical Intervention in Nonfunctioning Pituitary Macroadenomas in Adult Patients without Optic Apparatus Compression-Should We Consider It? A Matched Case-Control Study.

BACKGROUND: Surgical decompression is the recommended treatment for patients with nonfunctioning pituitary macroadenomas (NFPMAs) with associated visual impairment. Other relative indications for surgery include endocrinopathies, craniopathies, and headaches. Nevertheless, patients without these classical indications who would otherwise be considered asymptomatic with regard to the NFPMA and treated conservatively with clinical radiological surveillance may experience higher rates of other morbidities related to the NFPMA. We aimed to evaluate the prevalence of newly diagnosed comorbidities in conservatively treated patients with NFPMAs. METHODS: We reviewed the medical records of 55 patients with NFPMAs from 2012 to 2022 who lacked classical indications for surgery at diagnosis. During the follow-up period, we searched for any of the following potentially associated newly reported symptoms and signs: headache, dizziness, syncope, gastrointestinal symptoms, hyponatremia, falls, weakness and general deterioration, cerebrovascular accident-related symptoms, and endocrine-related symptoms including type 2 diabetes mellitus. Patients were compared with a matched control group. Cohort patients were further analyzed to detect specific endocrine axis deficiencies, and tumor volumes were measured using magnetic resonance imaging at diagnosis. RESULTS: The final cohort included 55 patients. NFPMAs were associated with the development of newly diagnosed headaches, hypertension, and hypopituitarism. Other symptoms associated with NFPMAs included dizziness, syncope/presyncope, gastrointestinal-related symptoms, hyponatremia, general weakness and falls, and infection-related symptoms. Average associated emergency department visits in this group were higher compared with the control group. CONCLUSIONS: These results may suggest the advantages of early surgical intervention for NFPMAs to mitigate comorbidities and improve health-related quality of life.

Personalizing non-small cell lung cancer treatment through patient-derived xenograft models: preclinical and clinical factors for consideration.

PURPOSE: In the pursuit of creating personalized and more effective treatment strategies for lung cancer patients, Patient-Derived Xenografts (PDXs) have been introduced as preclinical platforms that can recapitulate the specific patient's tumor in an in vivo model. We investigated how well PDX models can preserve the tumor's clinical and molecular characteristics across different generations. METHODS: A Non-Small Cell Lung Cancer (NSCLC) PDX model was established in NSG-SGM3 mice and clinical and preclinical factors were assessed throughout subsequent passages. Our cohort consisted of 40 NSCLC patients, which were used to create 20 patient-specific PDX models in NSG-SGM3 mice. Histopathological staining and Whole Exome Sequencing (WES) analysis were preformed to understand tumor heterogeneity throughout serial passages. RESULTS: The main factors that contributed to the growth of the engrafted PDX in mice were a higher grade or stage of disease, in contrast to the long duration of chemotherapy treatment, which was negatively correlated with PDX propagation. Successful PDX growth was also linked to poorer prognosis and overall survival, while growth pattern variability was affected by the tumor aggressiveness, primarily affecting the first passage. Pathology analysis showed preservation of the histological type and grade; however, WES analysis revealed genomic instability in advanced passages, leading to the inconsistencies in clinically relevant alterations between the PDXs and biopsies. CONCLUSIONS: Our study highlights the impact of multiple clinical and preclinical factors on the engraftment success, growth kinetics, and tumor stability of patient-specific NSCLC PDXs, and underscores the importance of considering these factors when guiding and evaluating prolonged personalized treatment studies for NSCLC patients in these models, as well as signaling the imperative for additional investigations to determine the full clinical potential of this technique.

Pharmacokinetics of glutamate-oxaloacetate transaminase and glutamate-pyruvate transaminase and their blood glutamate-lowering activity in naïve rats.

Traumatic brain injury (TBI) and stroke lead to elevated levels of glutamate in the brain that negatively affect the neurological outcomes in both animals and humans. Intravenous administration of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) enzymes can be used to lower the blood glutamate levels and to improve the neurological outcome following TBI and stroke. The objective of this study was to analyze the pharmacokinetics and to determine the glutamate-lowering effects of GOT and GPT enzymes in naïve rats. We determined the time course of serum GOT, GPT, and glutamate levels following a single intravenous administration of two different doses of each one of the studied enzymes. Forty-six male rats were randomly assigned into one of 5 treatment groups: saline (control), human GOT at dose 0.03 and 0.06 mg/kg and porcine GPT at dose 0.6 and 1.2 mg/kg. Blood samples were collected at baseline, 5 min, and 2, 4, 8, 12, and 24 h after the drug injection and GOT, GPT and glutamate levels were determined. The pharmacokinetics of both GOT and GPT followed one-compartment model, and both enzymes exhibited substantial glutamate-lowering effects following intravenous administration. Analysis of the pharmacokinetic data indicated that both enzymes were distributed predominantly in the blood (central circulation) and did not permeate to the peripheral organs and tissues. Several-hour delay was present between the time course of the enzyme levels and the glutamate-lowering effects (leading to clock-wise hysteresis on concentration-effect curves), apparently due to the time that is required to affect the pool of serum glutamate. We conclude that the interaction between the systemically-administered enzymes (GOT and GPT) and the glutamate takes place in the central circulation. Thus, glutamate-lowering effects of GOT and GPT apparently lead to redistribution of the excess glutamate from the brain's extracellular fluid into the blood and can reduce secondary brain injury due to glutamate neurotoxicity. The outcomes of this study regarding the pharmacokinetic and pharmacodynamic properties of the GOT and GPT enzymes will be subsequently verified in clinical studies that can lead to design of effective neuroprotective treatment strategies in patients with traumatic brain diseases and stroke.

Frequency- and spike-timing-dependent mitochondrial Ca2+ signaling regulates the metabolic rate and synaptic efficacy in cortical neurons.

Mitochondrial activity is crucial for the plasticity of central synapses, but how the firing pattern of pre- and postsynaptic neurons affects the mitochondria remains elusive. We recorded changes in the fluorescence of cytosolic and mitochondrial Ca2+ indicators in cell bodies, axons, and dendrites of cortical pyramidal neurons in mouse brain slices while evoking pre- and postsynaptic spikes. Postsynaptic spike firing elicited fast mitochondrial Ca2+ responses that were about threefold larger in the somas and apical dendrites than in basal dendrites and axons. The amplitude of these responses and metabolic activity were extremely sensitive to the firing frequency. Furthermore, while an EPSP alone caused no detectable Ca2+ elevation in the dendritic mitochondria, the coincidence of EPSP with a backpropagating spike produced prominent, highly localized mitochondrial Ca2+ hotspots. Our results indicate that mitochondria decode the spike firing frequency and the Hebbian temporal coincidences into the Ca2+ signals, which are further translated into the metabolic output and most probably lead to long-term changes in synaptic efficacy.

Visualization of both proximal M2-MCA segments in patients (the Tilted-V Sign) with acute M1-MCA occlusion stroke is associated with better procedural and prognostic outcomes.

Introduction: We aimed to assess the clinical significance of M1-MCA occlusion with visualization of both MCA-M2 segments ["Tilted-V sign" (TVS)] on initial CT angiography (CTA) in patients with acute ischemic stroke (AIS) undergoing endovascular thrombectomy (EVT). Methods: Data for patients with consecutive AIS undergoing EVT for large vessel occlusion (LVO) in two academic centers are recorded in ongoing databases. Patients who underwent EVT for M1-MCA occlusions ≤ 6 h from symptom onset were included in this retrospective analysis. Results: A total of 346 patients met the inclusion criteria; 189 (55%) had positive TVS. Patients with positive TVS were younger (68 ± 14 vs. 71 ± 14 years, P = 0.028), with similar rates of vascular risk factors and baseline modified Rankin scores (mRS) 0-2. The rates of achieving thrombolysis in cerebral ischemia (TICI) 2b-3 were similar to the two groups (79%), although successful first-pass recanalization was more common with TVS (64 vs. 36%, p = 0.01). On multivariate analysis, higher collateral score [odds ratio (OR) 1.38 per unit increase, p = 0.008] and lower age (OR 0.98 per year increase, p = 0.046) were significant predictors of TVS. Patients with positive TVS had higher post-procedural Alberta Stroke Program Early CT Score (ASPECTS; 6.9 ± 2.2 vs. 5.2 ± 2.3, p = 0.001), were discharged with lower National Institutes of Health Stroke Score (NIHSS; 6±6 vs. 9±7, p = 0.003) and higher rates of mRS 0-2 (29.5 vs. 12%, p = 0.001), and had lower rates of 90-day mortality (13.2 vs. 21.6%, p = 0.038). However, TVS was not an independent predictor of functional independence (OR 2.51; 95% CI 0.7-8.3). Conclusion: Tilted-V Sign, an easily identifiable radiological marker, is associated with fewer recanalization attempts, better functional outcomes, and reduced mortality.

Pyruvate's blood glutamate scavenging activity contributes to the spectrum of its neuroprotective mechanisms in a rat model of stroke.

In previous studies, we have shown that by increasing the brain-to-blood glutamate efflux upon scavenging blood glutamate with either oxaloacetate or pyruvate, one achieves highly significant neuroprotection particularly in the context of traumatic brain injury. The current study examines, for the first time, how the blood glutamate scavenging properties of glutamate-pyruvate transaminase (GPT), alone or in combination with pyruvate, may contribute to the spectrum of its neuroprotective mechanisms and improve the outcome of rats exposed to brain ischemia, as they do after head trauma. Rats that were exposed to permanent middle cerebral artery occlusion (MCAO) and treated with intravenous 250 mg/kg pyruvate had a smaller volume of infarction and reduced brain edema, resulting in an improved neurological outcome and reduced mortality compared to control rats treated with saline. Intravenous pyruvate at the low dose of 31.3 mg/kg did not demonstrate any neuroprotection. However, when combined with 0.6 mg/kg of GPT there was a similar neuroprotection observed as seen with pyruvate at 250 mg/kg. Animals treated with 1.69 g/kg glutamate had a worse neurological outcome and a larger extent of brain edema. The decrease in mortality, infarcted brain volume and edema, as well as the improved neurological outcome following MCAO, was correlated with a decrease in blood glutamate levels. We therefore suggest that the blood glutamate scavenging activity of GPT and pyruvate contributes to the spectrum of their neuroprotective mechanisms and may serve as a new neuroprotective strategy for the treatment of ischemic stroke.

Tumor-Treating Fields for the treatment of glioblastoma: a systematic review and meta-analysis.

BACKGROUND: Tumor-Treating Fields (TTFields) is an emerging treatment modality for glioblastoma (GBM). Studies have shown a good safety profile alongside improved efficacy in newly diagnosed GBM (ndGBM), while a less clear effect was shown for recurrent GBM (rGBM). Despite regulatory support, sectors of the neuro-oncology community have been reluctant to accept it as part of the standard treatment protocol. To establish an objective understanding of TTFields' mechanism of action, safety, efficacy, and economical implications, we conducted a systematic literature review and meta-analysis. METHODS: A systematic search was conducted in PubMed, Scopus, and Cochrane databases. Twenty studies met the pre-defined inclusion criteria, incorporating 1636 patients (542 ndGBM and 1094 rGBM), and 11 558 patients (6403 ndGBM and 5155 rGBM) analyzed for the clinical outcomes and safety endpoints, respectively. RESULTS: This study demonstrated improved clinical efficacy and a good safety profile of TTFields. For ndGBM, pooled median overall survival (OS) and progression-free survival (PFS) were 21.7 (95%CI = 19.6-23.8) and 7.2 (95%CI = 6.1-8.2) months, respectively. For rGBM, pooled median OS and PFS were 10.3 (95%CI = 8.3-12.8) and 5.7 (95%CI = 2.8-10) months, respectively. Compliance of ≥75% was associated with an improved OS and the predominant adverse events were dermatologic, with a pooled prevalence of 38.4% (95%CI = 32.3-44.9). Preclinical studies demonstrated TTFields' diverse molecular mechanism of action, its potential synergistic efficacy, and suggest possible benefits for certain populations. CONCLUSIONS: This study supports the use of TTFields for GBM, alongside the standard-of-care treatment protocol, and provides a practical summary, discussing the current clinical and preclinical aspects of the treatment and their implication on the disease course.

A Novel Histological Technique to Assess Severity of Traumatic Brain Injury in Rodents: Comparisons to Neuroimaging and Neurological Outcomes.

Here we evaluate an alternative protocol to histologically examine blood-brain barrier (BBB) breakdown, brain edema, and lesion volume following traumatic brain injury (TBI) in the same set of rodent brain samples. We further compare this novel histological technique to measurements determined by magnetic resonance imaging (MRI) and a neurological severity score (NSS). Sixty-six rats were randomly assigned to a sham-operated, mild TBI, moderate TBI, or severe TBI group. 48 h after TBI, NSS, MRI and histological techniques were performed to measure TBI severity outcome. Both the histological and MRI techniques were able to detect measurements of severity outcome, but histologically determined outcomes were more sensitive. The two most sensitive techniques for determining the degree of injury following TBI were NSS and histologically determined BBB breakdown. Our results demonstrate that BBB breakdown, brain edema, and lesion volume following TBI can be accurately measured by histological evaluation of the same set of brain samples.

Successful management of spinal cord ischemia in a pediatric patient with fibrocartilaginous embolism: illustrative case.

BACKGROUND: Fibrocartilaginous embolism (FCE) is a rare cause of ischemic myelopathy that occurs when the material of the nucleus pulposus migrates into vessels supplying the spinal cord. The authors presented a case of pediatric FCE that was successfully managed by adapting evidence-based recommendations used for spinal cord neuroprotection in aortic surgery. OBSERVATIONS: A 7-year-old boy presented to the emergency department with acute quadriplegia and hemodynamic instability that quickly progressed to cardiac arrest. After stabilization, the patient regained consciousness but remained in a locked-in state with no spontaneous breathing. The patient presented a diagnostic challenge. Traumatic, inflammatory, infectious, and ischemic etiologies were considered. Eventually, the clinical and radiological findings led to the presumed diagnosis of FCE. Treatment with continuous cerebrospinal fluid drainage (CSFD), pulse steroids, and mean arterial pressure augmentation was applied, with subsequent considerable and consistent neurological improvement. LESSONS: The authors proposed consideration of the adaptation of spinal cord neuroprotection principles used routinely in aortic surgery for the management of traumatic spinal cord ischemia (FCE-related in particular), namely, permissive arterial hypertension and CSFD. This is hypothesized to allow for the maintenance of sufficient spinal cord perfusion until adequate physiological blood perfusion is reestablished (remodeling of the collateral arterial network and/or clearing/absorption of the emboli).

A Complex Diving-For-Food Task to Investigate Social Organization and Interactions in Rats.

For many species, where status is a vital motivator that can affect health, social hierarchies influence behavior. Social hierarchies that include dominant-submissive relationships are common in both animal and human societies. These relationships can be affected by interactions with others and with their environment, making them difficult to analyze in a controlled study. Rather than a simple dominance hierarchy, this formation has a complicated presentation that allows rats to avoid aggression. Status can be stagnant or mutable, and results in complex societal stratifications. Here we describe a complex diving-for-food task to investigate rodent social hierarchy and behavioral interactions. This animal model may allow us to assess the relationship between a wide range of mental illnesses and social organization, as well as to study the effectiveness of therapy on social dysfunction.

A Metric Test for Assessing Spatial Working Memory in Adult Rats following Traumatic Brain Injury.

Impairments to sensory, short-term, and long-term memory are common side effects after traumatic brain injury (TBI). Due to the ethical limitations of human studies, animal models provide suitable alternatives to test treatment methods, and to study the mechanisms and related complications of the condition. Experimental rodent models have historically been the most widely used due to their accessibility, low cost, reproducibility, and validated approaches. A metric test, which tests the ability to recall the placement of two objects at various distances and angles from one another, is a technique to study impairment in spatial working memory (SWM) after TBI. The significant advantages of metric tasks include the possibility of dynamic observation, low cost, reproducibility, relative ease of implementation, and low stress environment. Here, we present a metric test protocol to measure impairment of SWM in adult rats after TBI. This test provides a feasible way to evaluate physiology and pathophysiology of brain function more effectively.

[Urgent removal of ruptured cerebral arteriovenous malformations in children].

In 60-80% of children with arteriovenous malformation (AVM), the first manifestation is an abrupt rupture resulting in intracranial hemorrhage. Some cases of acute rupture result in compressive hematoma, severe mass effect and comatose patients. Acute surgery on cerebral arteriovenous malformations (AVMs) has seldom been reported or used. The authors present case reports of 3 children (ages: five months, 7 and 9 years) who underwent craniotomy for intraparenchymal hematoma evacuation and AVM removal within a few hours of bleeding. All 3 children arrived with decreased Levels of consciousness and rapid neurological deterioration. The 5 months old boy also suffered hypovolemic shock. The fast neurological worsening and mass effect of the extensive intracerebral hemorrhage prompted early surgical treatment. Due to active bleeding from the AVM, it was already resected in the acute stage using minimal invasive techniques. After one year of follow-up, all 3 children fully recovered with no neurological deficit. Post-operative angiography was performed to confirm that the malformation was totally removed. The management of AVM should include formal angiography, with or without endovascular embolization and late surgery when indicated. In this report, the authors presented 3 children who underwent urgent resection of the lesion with full neurological recovery. The management of AVM is reviewed with comparisons between surgical resection in the acute phase versus the late phase.

Single root multiple spinal schwannomas: Case report, treatment strategy and review of literature.

INTRODUCTION: Schwannomatosis is defined as multiple schwannomas without presence of neurofibromatosis and is a rare pathology. In vast majority of cases the schwannomas grow from different nerve roots or peripheral nerves. PRESENTATION OF CASE: A 52-year-old woman presented with multiple intradural schwannomas arranged in a chain along the spinal canal causing significant compression. The lesions were successfully removed using a left side en-bloc hemilaminectomy technique in order to preserve maximal stability of the posterior column. Back and leg pain resolved completely. Tendon reflexes returned to normal shortly. There was decreased pain sensation in the distribution of the left L3 spinal root. DISCUSSION: The traditional surgical strategy for posterior approach by laminectomy or laminotomy is sometimes complicated with instability or deformation of the vertebral column that requires surgical stabilization. We performed a one side en-bloc hemilaminectomy thus maintaining the integrity of the muscles and ligaments on the opposite side and preserving maximal stability of the vertebral column. Densely adherent tumors required careful sharp dissection and separation under neurosurgical monitoring and stimulation for recognition and preservation of spinal roots. An additional tumor was discovered by exploration of the spinal canal using an endoscope. CONCLUSION: Multiple spinal cord schwannomas that are growing along the same part of the vertebral column can be safely removed by one-sided hemilaminectomy with preservation of the integrity of the muscles and ligaments on the opposite side and thus maintain spinal stability. The 30° endoscope can be a good tool for visual exploration of the spinal canal.

Measuring Post-Stroke Cerebral Edema, Infarct Zone and Blood-Brain Barrier Breakdown in a Single Set of Rodent Brain Samples.

One of the most common causes of morbidity and mortality worldwide is ischemic stroke. Historically, an animal model used to stimulate ischemic stroke involves middle cerebral artery occlusion (MCAO). Infarct zone, brain edema and blood-brain barrier (BBB) breakdown are measured as parameters that reflect the extent of brain injury after MCAO. A significant limitation to this method is that these measurements are normally obtained in different rat brain samples, leading to ethical and financial burdens due to the large number of rats that need to be euthanized for an appropriate sample size. Here we present a method to accurately assess brain injury following MCAO by measuring infarct zone, brain edema and BBB permeability in the same set of rat brains. This novel technique provides a more efficient way to evaluate the pathophysiology of stroke.

Minimally Invasive Subtemporal Intradural Approach for Penetrating Orbitocranial Injury by Wooden Foreign Body Into the Lateral Wall of the Cavernous Sinus.

Non-missile transorbital penetrating head injuries are relatively rare, though potentially fatal injuries. Trajectory for intracranial entrance is typically via the orbital roof, the superior orbital fissure (SOF), or the optic canal. Non-metallic intracranial penetrating injuries are even scarcer and may pose unusual diagnostic and surgical challenges. Here we present and discuss a unique case of a penetrating injury by a wooden foreign body (FB) which entered and expanded the inter-dural space of the lateral cavernous sinus (CS) sinus wall without intracavernous or intradural involvement. The patient was a 71 year-old male who fell face-down and sustained a penetrating transorbital injury by a dry twig fragment, which passed through the SOF and into the interdural space of lateral wall of the ipsilateral CS. The patient was fully conscious (GCS15) at presentation but had severe ocular injury (complete ophthalmoplegia and blindness of the injured eye). The wooden FB was successfully removed via a minimally invasive subtemporal intradural approach with no apparent immediate or long-term complications. We emphasize the unusual diagnostic and surgical challenges related to this kind of rare injuries as reflected by the decision-making considerations taken in the presented case.

Inducing Acute Liver Injury in Rats via Carbon Tetrachloride (CCl4) Exposure Through an Orogastric Tube.

Acute liver injury (ALI) plays a crucial role in the development of hepatic failure, which is characterized by severe liver dysfunction including complications such as hepatic encephalopathy and impaired protein synthesis. Appropriate animal models are vital to test the mechanism and pathophysiology of ALI and investigate different hepatoprotective strategies. Due to its ability to perform chemical transformations, carbon tetrachloride (CCl4) is widely used in the liver to induce ALI through the formation of reactive oxygen species. CCl4 exposure can be performed intraperitoneally, by inhalation, or through a nasogastric or orogastric tube. Here, we describe a rodent model, in which ALI is induced by CCl4 exposure through an orogastric tube. This method is inexpensive, easily performed, and has minimal hazard risk. The model is highly reproducible and can be widely used to determine the efficacy of potential hepatoprotective strategies and assess markers of liver injury.