Alzheimer's disease (AD) is the foremost cause of dementia among other neurodegenerative diseases, leading to memory loss and cognitive deficits. AD has gained extensive attention in research for exploring possible interventions. One promising field is natural substances and compounds that could provide a wide range of neuroprotection against AD. This study aimed to investigate the possible effects of melatonin (MEL) and resveratrol (RES) in improving memory deficits in a sporadic mouse model of AD. Memory deficit was induced using AlCl3 and d-galactose for generating an AD mouse model. Mice were randomly distributed into five groups (n = 13): control, AD, AD + MEL (AD mice treated with 80 mg/kg of MEL), AD + RES (AD mice treated with 40 mg/kg of RES), and AD + Combination)AD mice that received 80 mg/kg MEL and 40 mg/kg RES). A novel object recognition task (NORT) and passive avoidance task (PAT) were used for assessing memory. Moreover, acetylcholinesterase (AChE) level, brain-derived neurotrophic factor (BDNF), and cAMP-response element binding (CREB) protein expression were measured in the prefrontal cortex tissue. Our results showed that MEL significantly improved memory deficits in both the NORT and PAT of the AD model, while RES improved the PAT only in the AD model. Co-treatment with MEL and RES exerted beneficial additive effects on recognition memory impairment in the AD mouse model. Moreover, our results demonstrated that both MEL and RES enhanced the cholinergic system and BDNF and CREB signaling pathways in the prefrontal cortex in an AD mouse model.

Background: The most prevalent malignant tumor of the CNS in adults is glioblastoma. Despite undergoing surgery and chemoradiotherapy, the prognosis remains unfavorable, with a median survival period ranging between 15 and 20 months. The incidence of glioblastoma metastasis outside CNS is uncommon with only 0.4%–2% reported rate, compared to other tumors that exhibit a 10% incidence rate of metastasis to the brain. On average, it takes about 11 months from the time of initial diagnosis for the tumor to spread beyond CNS. Consequently, the prognosis for metastatic glioblastoma is grim, with a 6‐month survival rate following diagnosis.Findings: The rarity of extracranial metastasis is attributed to the blood–brain barrier and lack of a lymphatic drainage system, although rare cases of hematogenous spread and direct implantation have been reported. The possible mechanisms remain unclear and require further investigation. Risk factors have been widely described, including previous craniotomy or biopsies, ventricular shunting, young age, radiation therapy, prolonged survival time, and tumor recurrence. Due to the lack of understanding about extracranial metastasis of glioblastoma pathogenesis, no effective treatment exists to date. Aggressive chemotherapies are not recommended for metastatic glioblastoma as their side effects may worsen the patient prognosis.Conclusion: The optimal treatment for extracranial metastasis of glioblastoma requires further investigation with a wide inclusion of patients. This review discusses the possible causes, factors, and underlying mechanisms of glioblastoma metastasis to different organs.

The aim of this study is to investigate the relationship between isocitrate dehydrogenase-1 (IDH1) mutation and O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylation with recurrence-free interval in glioblastoma patients treated with chemoradiotherapies. Clinical data were collected from 82 patients with totally resected glioblastoma and treated with adjuvant therapies from 2014 to 2019. IDH1 mutation was assessed by immunohistochemistry and MGMT promoter methylation was assessed by different sequencing methods. IDH1 mutation was present in 32 cases and 50 cases were IDH1 wildtype; 54 and 28 patients had unmethylated and methylated MGMT promoter, respectively, Of the 82 patients, 62 patients received chemoradiotherapy while 20 patients only received radiation. Approximately, 61% of patients had a tumor recurrence after 1 year, and 39% showed a recurrence before 1 year of treatment. There was no significant relationship between IDH1 mutation and MGMT promoter methylation (p-value = 0.972). Patients with IDH1 mutation and their age <50 years showed a significant difference in recurrence-free interval (p-value = 0.014). Difference in recurrence-free interval was also statistically observed in patients with unmethylated MGMT promoter and treated with chemoradiotherapies (p-value = 0.031), by which they showed a late tumor recurrence (p-value = 0.016). This revealed that IDH1 mutation and MGMT methylation are independent prognostic factors in glioblastoma. Although IDH1-mutant glioblastomas showed late tumor recurrence in patients less than 50 years old, the type of treatment modalities may not show additional beneficial outcome. Patients with unmethylated MGMT and IDH1 mutation, treated with different chemoradiotherapies, showed a late tumor recurrence.

Simple approach for the histomolecular diagnosis of central nervous system gliomas based on 2021 World Health Organization Classification

Objective: Intraoperative frozen section (IOFS) diagnosis of brain tumors plays an important role in assessing the adequacy of the sample and determining the treatment plan. The aim of this study was to investigate the diagnostic accuracy between IOFS and permanent sections.

Background: Tumour associated macrophages (TAMs) and tumour infiltrating lymphocytes (TILs) are considered dominant cells in glioblastoma microenvironment. Aim: The purpose of this study was to assess the expression of CD204^{+ M2}-polarized TAMs in glioblastomas and their relationship with CD4⁺TILs, Iba⁺microglia, and IDH1 mutation. We also exploreed the prognostic value of these markers on the recurrence-free interval (RFI). Methods: The expressions of CD204⁺TAMs, CD4⁺TILs, and Iba1⁺microglia were quantitively assessed in 45 glioblastomas using immunohistochemistry. Kaplan–Meier analysis and Cox hazards were used to examine the relationship between these factors. Results: CD204⁺TAMs were highly expressed in 32 tumours (71%) and the remaining 13 tumours (29%) had reduced expression. CD4⁺TILs were highly expressed in 10 cases (22%) and 35 cases (77.8%) had low expression. There was an inverse correlation between CD204⁺TAMs and CD4⁺TILs, in which 85% of tumours had a high expression of CD204⁺TAMs and a low expression of CD4⁺TILs. Nevertheless, there was no significant difference in IDH1 mutation status between the two groups (p = 0.779). There was a significant difference in Iba1⁺microglial activation between IDH1^mutant and IDH1^wildtype groups (p = 0.031). For cases with a high expression of CD204⁺TAMs and a low expression of CD4⁺TILs, there was a significant difference in RFI after treatment with chemoradiotherapy or radiotherapy (p = 0.030). Conclusion: Glioblastoma with a dense CD204⁺TAMs and few CD4⁺TILs is associated with IDH1^wildtype. These findings suggest that TAMs masks tumour cell and suppress T-cell tumoricidal functions via immunomodulatory mechanisms. Blockade of the CD204-TAM receptor may prevent this mechanism and allow the evolution of TILs.