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Background: The blood-brain barrier (BBB) impedes the passage of most circulating drugs into the brain. Low-intensity pulsed ultrasound with microbubbles (LIPU/MB) transiently opens the BBB, improving parenchymal drug penetration. Parenchymal drug permanence upon short-lived BBB opening is unknown. We compared the parenchymal permanence of temozolomide, carboplatin, and fluorescein, and investigated the effect of LIPU/MB on the concentration of carboplatin and fluorescein., Methods: We analyzed four patients who underwent intraoperative LIPU/MB with intravenous administration of carboplatin and fluorescein in the NCT04528680 clinical trial. Microdialysis catheters were implanted into sonicated and non-sonicated brain and measured drug levels over 24 hours. Published data from a microdialysis study of temozolomide without LIPU/MB were used for comparison., Results: LIPU/MB led to sustained elevated parenchymal drug concentrations, achieving 3.1-fold increase in brain-to-plasma AUC for carboplatin and fluorescein (P = 0.03). Compared to non-sonicated brain, sonicated brain had higher concentrations of carboplatin for 11 hours, and fluorescein for 5 hours. Drug levels in the sonicated brain exceeded their plasma concentrations at 21 hours and 7 hours, for carboplatin and fluorescein, respectively. In non-sonicated brain, drug half-life was longest for fluorescein (13.6 ± 11.0 hours), followed by carboplatin (5.1 ± 1.9 hours) and temozolomide (2.9 ± 1.6 hours). Sonication did not affect parenchymal drug half-life., Conclusion: Following LIPU/MB, BBB-impermeable drugs exhibit sustained elevated parenchymal concentrations surpassing their plasma levels, highlighting the bi-directional restriction of drug passage by the BBB. Future studies are warranted to explore drug trapping and the efficacy of sustained exposure to cytotoxic drugs for the treatment of brain-infiltrating tumors.

Objective: To evaluate the short-term surgical outcomes and the reimbursement patterns, after treatment of type 2 odontoid fractures using the anterior or posterior approach., Methods: The National Surgical Quality Improvement Program database was queried for surgically treated patients with type 2 odontoid fractures by the anterior or posterior approach between 2016 and 2020. Propensity score matching with the optimal approach was used to balance the cohorts., Results: A total of 96 patients in the anterior and 352 patients in the posterior surgery group were included in the unmatched analysis. After propensity score matching 1:1, 96 anterior and 96 posterior cases were included in the matched analysis. Operative times were shorter in the anterior group (92.0 vs. 145.0 minutes, P < 0.001). The need for intraoperative or postoperative transfusions was higher in the posterior group (15% vs. 2.1%; P = 0.002). However, there were no significant differences in complications between groups (P > 0.05). Hospital stay was significantly longer in the posterior group (4.5 days vs. 3.0; P = 0.049). Nonroutine discharge was more frequent in the posterior group (55% vs. 40%, P = 0.030). However, the rate of 30-day readmission, reoperation, and mortality did not differ between groups (P > 0.05). Also, the work relative value units were significantly higher in the anterior group (22.7 vs. 20.6, P < 0.001), indicating higher reimbursement trends for this approach., Conclusions: In this matched analysis, the anterior approach for type 2 odontoid fractures was superior to the posterior approach. The anterior approach was associated with significantly shorter operation times, hospital stays, fewer transfusions, nonroutine discharges, and higher reimbursements., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Vertebral artery injury (VAI) because of traumatic subaxial cervical spine injury is a rare but potentially devastating condition as it could lead to stroke. The aim of this study was to examine the incidence, risk factors, outcomes, and radiographic predictors of VAI in patients surgically treated for subaxial cervical spine injuries at a tertiary care trauma center., Methods: This is a retrospective population-based cohort study, including all patients surgically treated for traumatic subaxial cervical spine injuries at the study center between 2006 and 2018. Primary outcomes included mortality and morbidity after the injury. Propensity score matching, survival, univariable, and multivariable analyses were used to study the outcomes of interest., Results: Traumatic VAI primarily occurred after high-energy traumas such as motor vehicle accidents and falls from heights. The median age was 64.4 years (47.4-69.1), and 69% were male. In the cohort of patients with subaxial cervical injury, 54% had a spinal cord injury (SCI). In the subgroup with VAI, the frequency of SCI was 66% and a concomitant SCI and VAI were associated with a more severe American Spinal Cord Injury Association Impairment Scale grade (P = .015). However, after accounting for age, sex, and associated injuries, VAI did not affect postoperative complications, short- or long-term outcomes, or mortality rates. Facet joint dislocation was a unique radiographic predictor of VAI (odds ratio 3.8 [CI 1.42-10.7], P = .009)., Conclusion: The findings suggest that clinical outcomes of patients with traumatic cervical spine injuries were not negatively affected by the presence of a VAI. Several radiographic factors were associated with VAI; however, only facet joint dislocation remained as an independent predictor of this injury., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Objective: Neurosurgery is one of the most competitive specialties, and navigating the match process is often challenging for aspiring applicants. Here, we analyze insights from the National Resident Matching Program Director Surveys, illustrating evolving trends in applicant selection for interviews and for the ranking process, and providing a comparison with other specialties., Methods: We evaluated 7 surveys administered from 2012 to 2022. Six biennial surveys reported on factors influencing interview and ranking processes, while all 7 surveys included data about the program director (PD)'s attitude toward United States Medical Licensing Examination (USMLE) test scores., Results: The response rate of PDs decreased over the years. The most cited factor for interviews included specialty-specific recommendation letters (95%), USMLE Step 1 scores (91%), and interest in research (78%). A recent decline in emphasis on USMLE Step 1 scores coincided with a growing reliance on USMLE Step 2 scores. Award in basic science held significant esteem to a subset of programs. Personal characteristics dominated for ranking, with faculty interaction (89%), interpersonal skills (89%), and house staff interaction (85%) being the most important. Yet, PDs reported a difficulty in assessing interpersonal skills through virtual interviews., Conclusions: Our analysis revealed the pervasive importance of specialized endorsements and academic achievements when screening applicants for the interview process. A shift in emphasis toward the USMLE Step 2 became apparent. Personal characteristics, on the other hand, seemed crucial to make a match and rank high among the pool of interviewed applicants. We uncovered difficulties in assessing these characteristics through virtual interviews., (Copyright © 2024. Published by Elsevier Inc.)

Background and Objectives: Carotid endarterectomy (CEA) is a well-established treatment option for carotid stenosis. The choice between general anesthesia (GA) and nongeneral anesthesia (non-GA) during CEA remains a subject of debate, with concerns regarding perioperative complications, particularly myocardial infarctions. This study aimed to evaluate the outcomes associated with GA vs non-GA CEA using a large, nationwide database., Methods: The National Surgical Quality Improvement Project database was queried for patients undergoing CEA between 2013 and 2020. Primary outcome measures including surgical outcomes and 30-day postoperative complications were compared between the 2 anesthesia methods, after 2:1 propensity score matching., Results: After propensity score matching, a total of 25 356 patients (16 904 in the GA and 8452 in the non-GA group) were included. Non-GA compared with GA CEA was associated with significantly shorter operative times (101.9, 95% CI: 100.5-103.3 vs 115.8 95% CI: 114.4-117.2 minutes, P < .001), reduced length of hospital stays (2.3, 95% CI: 2.15-2.4 vs 2.5, 95% CI: 2.4-2.6 days, P < .001), and lower rates of 30-day postoperative complications, including myocardial infarctions (0.8% vs 1.2%, P = .003), unplanned intubations (0.8% vs 1.1%, P = .016), pneumonia (0.5% vs 1%, P < .001), and urinary tract infections (0.4% vs 0.7%, P = .003). These outcomes were notably more pronounced in the younger (≤70 years) and high morbidity (American Society of Anesthesiologists 3-5) cohorts., Conclusion: In this nationwide registry-based study, non-GA CEA was associated with better short-term outcomes in terms of perioperative complications, compared with GA CEA. The findings suggest that non-GA CEA may be a safer alternative, especially in younger patients and those with more comorbidities., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Purpose: We aimed to investigate surgical outcomes in octogenarians with subaxial cervical spine injuries and determine the predictors of complications and mortality., Methods: Eligible for inclusion were all patients surgically treated between 2006 and 2018, with either anterior or posterior fixation for subaxial spine injuries. A cohort of octogenarians was identified and matched 1:1 to a corresponding cohort of younger adults. Primary outcomes were perioperative complications and mortality., Results: Fifty-four patients were included in each of the octogenarian and younger groups (median age: 84.0 vs. 38.5). While the risks for surgical complications, including dural tears and wound infections, were similar between groups, the risks of postoperative medical complications, including respiratory or urinary tract infections, were significantly higher among the elderly (p < 0.05). Additionally, there were no differences in operative time (p = 0.625) or estimated blood loss (p = 0.403) between groups. The 30 and 90-day mortality rates were significantly higher among the elderly (p = 0.004 and p < 0.001). These differences were due to comorbidities in the octogenarian cohort as they were revoked when propensity score matching was performed to account for the differences in American Society of Anesthesiology (ASA) grade. Multivariable logistic regression revealed age and ASA score to be independent predictors of complications and the 90-day mortality, respectively., Conclusions: Octogenarians with comorbidities were more susceptible to postoperative complications, explaining the increased short-term mortality in this group. However, octogenarians without comorbidities had similar outcomes compared to the younger patients, indicating that overall health, including comorbidities, rather than chronological age should be considered in surgical decision-making., (© 2024. The Author(s).)

Given the marginal penetration of most drugs across the blood-brain barrier, the efficacy of various agents remains limited for glioblastoma (GBM). Here we employ low-intensity pulsed ultrasound (LIPU) and intravenously administered microbubbles (MB) to open the blood-brain barrier and increase the concentration of liposomal doxorubicin and PD-1 blocking antibodies (aPD-1). We report results on a cohort of 4 GBM patients and preclinical models treated with this approach. LIPU/MB increases the concentration of doxorubicin by 2-fold and 3.9-fold in the human and murine brains two days after sonication, respectively. Similarly, LIPU/MB-mediated blood-brain barrier disruption leads to a 6-fold and a 2-fold increase in aPD-1 concentrations in murine brains and peritumoral brain regions from GBM patients treated with pembrolizumab, respectively. Doxorubicin and aPD-1 delivered with LIPU/MB upregulate major histocompatibility complex (MHC) class I and II in tumor cells. Increased brain concentrations of doxorubicin achieved by LIPU/MB elicit IFN-γ and MHC class I expression in microglia and macrophages. Doxorubicin and aPD-1 delivered with LIPU/MB results in the long-term survival of most glioma-bearing mice, which rely on myeloid cells and lymphocytes for their efficacy. Overall, this translational study supports the utility of LIPU/MB to potentiate the antitumoral activities of doxorubicin and aPD-1 for GBM., (© 2024. The Author(s).)

Purpose: We recently reported on clinical trials for patients with recurrent glioblastoma where low-intensity pulsed ultrasound and microbubbles (LIPU/MB) improved paclitaxel or carboplatin delivery into the brain. Here, we report variable local tumor control with paclitaxel at the maximal/target dose in our phase I trial (NCT04528680). To address this, we investigated the combination of paclitaxel with carboplatin in preclinical glioma models., Experimental Design: We performed MRI-based analysis to evaluate disease control in patients from our trial. We studied the cytotoxicity of paclitaxel and carboplatin against 11 human glioma lines as monotherapy and in combination at concentrations derived from human intraoperative studies. Synergy was assessed with the Loewe model and the survival benefit evaluated in two xenografts. We examined the effects on cell cycle progression, DNA damage, and apoptosis., Results: Patients treated with paclitaxel and LIPU/MB exhibited variable local tumor control, which correlated with overall survival. We observed limited cross-resistance to paclitaxel and carboplatin in glioma lines, with almost a third of them being exclusively susceptible to one drug. This combination led to susceptibility of 81% of lines and synergy in 55% of them. The combination proved more efficacious in two intracranial xenografts when administered with LIPU/MB, leading to complementary effects on cell cycle arrest., Conclusions: Combining paclitaxel and carboplatin in gliomas may be more efficacious than monotherapy, as in other cancers, due to synergy and independent susceptibility to each drug. These results form the basis for an ongoing phase II trial (NCT04528680) where we investigate this combination with LIPU/MB., (©2024 American Association for Cancer Research.)

We recently discovered a putative paclitaxel response predictive biomarker for glioblastoma and breast cancer using the whole genome CRISPR knockout screen. The biomarker candidate was validated in two independent breast cancer patient cohorts that received taxane treatment. To further evaluate the potential application of this biomarker in the clinic for patients with glioblastoma, a prospective validation in cohorts of patients with glioblastoma is essential and will be performed as part of our ongoing phase II clinical trial (NCT04528680). The validation of novel biomarkers of susceptibility to therapy is critical to elucidate the efficacy signal of therapeutic agents. This is especially important in the context of glioblastoma, where therapeutic benefit is variable and unpredictable, leading to negative trials, yet the outcome of subset of patients has outperformed expectations.

Purpose: Evidence suggests that MAPK pathway activation, as measured by ERK1/2 phosphorylation (p-ERK), predicts overall survival (OS) in patients with recurrent glioblastoma receiving anti-PD-1 therapy. We aimed to validate these findings in independent cohorts., Experimental Design: In a 24-patient clinical trial on recurrent glioblastoma and high-grade gliomas, we examined the link between p-ERK levels and OS. Patients received intravenous nivolumab, followed by maximal safe resection and an intracerebral injection of either ipilimumab alone or combined with nivolumab. Biweekly adjuvant nivolumab was then administered up to five times (NCT03233152). Using REporting recommendations for tumor MARKER prognostic studies (REMARK) criteria, we conducted independent analyses for p-ERK quantification and statistical evaluations. Additional comparative analysis included prior cohorts, totaling 65 patients. Cox proportional hazards models and meta-analysis were employed to assess p-ERK as a predictive biomarker after immunotherapy., Results: Lower median p-ERK+ cell density was observed compared with prior studies, likely due to variable tissue processing across cohorts. Nonetheless, high p-ERK was associated with prolonged OS, particularly in isocitrate dehydrogenase wild-type glioblastomas (P = 0.036). Median OS for high and low p-ERK patients were 55.6 and 30 weeks, respectively. Multivariable analysis reinforced p-ERK's significance in survival prediction (P = 0.011). Upon p-ERK normalization across cohorts (n = 65), meta-analysis supported the survival benefit of elevated tumor p-ERK levels (P = 0.0424)., Conclusions: This study strengthens the role of p-ERK as a predictive biomarker for OS in patients with glioblastoma on immune checkpoint blockade. Future research should focus on further validation in prospective trials and the standardization of preanalytical variables influencing p-ERK quantification., (©2023 American Association for Cancer Research.)

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality. The innate and adaptive immune responses play an important role in the pathogenesis of TBI. Gamma-delta (γδ) T cells have been shown to affect brain immunopathology in multiple different conditions, however, their role in acute and chronic TBI is largely unknown. Here, we show that γδ T cells affect the pathophysiology of TBI as early as one day and up to one year following injury in a mouse model. TCRδ -/- mice are characterized by reduced inflammation in acute TBI and improved neurocognitive functions in chronic TBI. We find that the Vγ1 and Vγ4 γδ T cell subsets play opposing roles in TBI. Vγ4 γδ T cells infiltrate the brain and secrete IFN-γ and IL-17 that activate microglia and induce neuroinflammation. Vγ1 γδ T cells, however, secrete TGF-β that maintains microglial homeostasis and dampens TBI upon infiltrating the brain. These findings provide new insights on the role of different γδ T cell subsets after brain injury and lay down the principles for the development of targeted γδ T-cell-based therapy for TBI., (© 2023. The Author(s).)

Glioblastoma is the most common and aggressive primary malignant brain tumour. The prognosis of patients with glioblastoma is poor, and their overall survival averages at 1 year, despite advances made in cancer therapy. The emergence of immunotherapy, a strategy that targets the natural mechanisms of immune evasion by cancerous cells, has revolutionised the treatment of melanoma, lung cancer and other solid tumours; however, immunotherapy failed to improve the prognosis of patients with glioblastoma. This is attributed to the fact that glioblastoma is endowed with numerous mechanisms of resistance that include the intrinsic resistance, which refers to the location of the tumour within the brain and the nature of the blood-brain barrier, as well as the adaptive and acquired resistance that result from the tumour heterogeneity and its immunosuppressive microenvironment. Glioblastoma is notorious for its inter and intratumoral heterogeneity, which, coupled with its spatial and temporal evolution, limits its immunogenicity. In addition, the tumour microenvironment is enriched with immunosuppressive cells and molecules that hinder the reactivity of cytotoxic immune cells and the success of immunotherapies. In this article, we review the mechanisms of resistance of glioblastoma to immunotherapy and discuss treatment strategies to overcome them worthy of further exploration., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The prevalence of obesity tripled worldwide between 1975 and 2016, and it is projected that half of the US population will be overweight by 2030. The obesity pandemic is attributed, in part, to the increasing consumption of the high-fat, high-carbohydrate Western diet, which predisposes to the development of the metabolic syndrome and correlates with decreased cognitive performance. In contrast, the high-fat, low-carbohydrate ketogenic diet has potential therapeutic roles and has been used to manage intractable seizures since the early 1920s. The brain accounts for 25% of total body glucose metabolism and, as a result, is especially susceptible to changes in the types of nutrients consumed. Here, we discuss the principles of brain metabolism with a focus on the distinct effects of the Western and ketogenic diets on the progression of neurological diseases such as epilepsy, Parkinson's disease, Alzheimer's disease, and traumatic brain injury, highlighting the need to further explore the potential therapeutic effects of the ketogenic diet and the importance of standardizing dietary formulations to assure the reproducibility of clinical trials., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objectives: Groundbreaking trials have shown the tremendous efficacy of mechanical thrombectomy for large vessel occlusions. Currently, mechanical thrombectomy is limited to patients with NIHSS scores ≥6. We investigated the feasibility and safety of MT in patients presenting with NIHSS scores <6., Materials and Methods: A retrospective review of patient who presented with acute ischemic stroke due to large vessel occlusion with an NIHSS score <6 between 2015 - 2021. The patients were then divided into two groups: those who received mechanical thrombectomy and those who did not., Results: Among 83 patients, 41 received a mechanical thrombectomy while 42 received medical treatment only. The mean age in the mechanical thrombectomy group was 66 years versus 60 years in the medical group (p = 0.06). Risk factors for stroke did not differ significantly between both groups. 14 patients (34.1%) in the mechanical thrombectomy group and 20 (47.6%) in the medical group received tissue plasminogen activator. No significant difference in clinical improvement (NIHSS) at discharge (p=0.85) or the mRS score at 90 days (p = 0.15) was noted. Mechanical thrombectomy was associated with smaller infarct size (p=0.04) and decreased mortality (p=0.03)., Conclusions: Mechanical thrombectomy is safe and effective for patients who present with large vessel occlusions and low initial NIHSS scores. Therefore, the decision to offer the patient mechanical thrombectomy or not should not be decided by NIHSS score alone. Rather, the decision should be multifactorial with the aim of maximizing the patients' outcomes., Competing Interests: Declaration of Competing Interest Dr. Jabbour is a consultant for Medtronic and MicroVention. Dr. Tjoumakaris and Dr. Gooch are consultants for Stryker. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. Dr. Abbas reports no disclosures Dr. Herial reports no disclosures Dr. El Naamani reports no disclosures Dr. Sweid reports no disclosures Dr. Weinberg reports no disclosures Mr. Habashy reports no disclosures Dr. Rosenwasser reports no disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) remains a significant leading cause of death and disability among adults and children globally. To date, there are no Food and Drug Administration-approved drugs that can substantially attenuate the sequelae of TBI. The innumerable challenges faced by the conventional de novo discovery of new pharmacological agents led to the emergence of alternative paradigm, which is drug repurposing. Repurposing of existing drugs with well-characterized mechanisms of action and human safety profiles is believed to be a promising strategy for novel drug use. Compared to the conventional discovery pathways, drug repurposing is less costly, relatively rapid, and poses minimal risk of the adverse outcomes to study on participants. In recent years, drug repurposing has covered a wide range of neurodegenerative diseases and neurological disorders including brain injury. This review highlights the advances in drug repurposing and presents some of the promising candidate drugs for potential TBI treatment along with their possible mechanisms of neuroprotection. Edaravone, glyburide, ceftriaxone, levetiracetam, and progesterone have been selected due to their potential role as putative TBI neurotherapeutic agents. These drugs are Food and Drug Administration-approved for purposes other than brain injuries; however, preclinical and clinical studies have shown their efficacy in ameliorating the various detrimental outcomes of TBI.

Background: The frontal bone is frequently approached during neurosurgical procedures. Feared complications of such surgeries include cerebrospinal fluid leak, among others, and frequently result from a breach of the frontal sinus. For this reason, the sinus should be avoided when possible. The supraorbital notch (SON) is a reliable and easily identifiable surgical landmark and its relation to the frontal sinus has been previously studied. However, the frontal sinus shows significant variability in size and shape between populations., Methods: In the present study, we investigate the frontal sinus dimension and its relation to the SON in the Middle Eastern population., Results: The analysis of a set of computed tomography scans reveals a significant variation in size between genders, and we subsequently provide neurosurgeons in the region with population-targeted, gender-specific risk maps., Conclusions: We finally conclude that a 2-cm margin rostral and lateral to the SON is safest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Edaravone is a potent free-radical scavenger that has been in the market for more than 30 years. It was originally developed in Japan to treat strokes and has been used there since 2001. Aside from its anti-oxidative effects, edaravone demonstrated beneficial effects on proinflammatory responses, nitric oxide production, and apoptotic cell death. Interestingly, edaravone has shown neuroprotective effects in several animal models of diseases other than stroke. In particular, edaravone administration was found to be effective in halting amyotrophic lateral sclerosis (ALS) progression during the early stages. Accordingly, after its success in Phase III clinical studies, edaravone has been approved by the FDA as a treatment for ALS patients. Considering its promises in neurological disorders and its safety in patients, edaravone is a drug of interest that can be repurposed for traumatic brain injury (TBI) treatment. Drug repurposing is a novel approach in drug development that identifies drugs for purposes other than their original indication. This review presents the biochemical properties of edaravone along with its effects on several neurological disorders in the hope that it can be adopted for treating TBI patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Traumatic brain injury (TBI) is a global health burden and a major cause of disability and mortality. An early cascade of physical and structural damaging events starts immediately post-TBI. This primary injury event initiates a series of neuropathological molecular and biochemical secondary injury sequelae, that last much longer and involve disruption of cerebral metabolism, mitochondrial dysfunction, oxidative stress, neuroinflammation, and can lead to neuronal damage and death. Coupled to these events, recent studies have shown that lifestyle factors, including diet, constitute additional risk affecting TBI consequences and neuropathophysiological outcomes. There exists molecular cross-talk among the pathways involved in neuronal survival, neuroinflammation, and behavioral outcomes, that are shared among western diet (WD) intake and TBI pathophysiology. As such, poor dietary intake would be expected to exacerbate the secondary damage in TBI. Hence, the aim of this review is to discuss the pathophysiological consequences of WD that can lead to the exacerbation of TBI outcomes. We dissect the role of mitochondrial dysfunction, oxidative stress, neuroinflammation, and neuronal injury in this context. We show that currently available data conclude that intake of a diet saturated in fats, pre- or post-TBI, aggravates TBI, precludes recovery from brain trauma, and reduces the response to treatment., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

The use of inducible transgenic Nestin-CreER T2 mice has proved to be an essential research tool for gene targeting and studying the molecular pathways implicated in adult neurogenesis, namely, inside the adult subgranular zone (SGZ) of the dentate gyrus and the adult subventricular zone (SVZ) lining the lateral ventricles. Several lines of Nestin-CreER-expressing mice were generated and used in adult neurogenesis research in the past two decades; however, their suitability for studying neurogenesis in aged mice remains elusive. Here, we assessed the efficiency of Cre-loxP genetic recombination in the aging SVZ using the Nestin-CreER T2 /Rosa26YFP line designed by Lagace et al. (J Neurosci 27(46):12623-12629, 2007). This analysis was performed in 12-month-old (middle-aged) mice and 20-month-old (old) mice compared to 2-month-old (young adult) mice. To evaluate successful recombination, our approach relies on the histological assessment of Cre mRNA level of expression and the YFP reporter gene's expression inside the aging SVZ by combining in situ hybridization and immunohistochemistry. Using co-immunolabeling, this approach also provides the advantage of estimating the percentage of recombined progeny [(GFP+Nestin+)/Nestin+] and the rate of cell proliferation [(GFP+Ki67+)/GFP+] inside the aging SVZ niche.