The fifth edition of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System (WHO CNS5) introduces a revised framework for classifying brain and spinal cord tumours, emphasizing the crucial role of molecular diagnostics in accurately identifying neoplasms. A key advancement in this edition is the clear distinction between paediatric-type diffuse low-grade gliomas (pDLGGs) and paediatric-type diffuse high-grade gliomas (pDHGGs) as separate tumour entities. Although histologically and morphologically similar, paediatric diffuse gliomas differ significantly from their adult counterparts in terms of molecular genetics, prognosis, and treatment approaches. The pDLGG category comprises four tumour types: diffuse astrocytoma with MYB- or MYBL1-alterations, angiocentric glioma, polymorphous low-grade neuroepithelial tumour of the young (PLNTY), and diffuse low-grade glioma with MAPK pathway alterations-three of which have been newly recognized. As imaging plays a critical role in the initial diagnosis, surgical planning, and post-treatment monitoring, it is essential for radiologists to be familiar with the imaging hallmarks that distinguish pDLGGs from other paediatric brain tumours, including high-grade gliomas and non-glial neoplasms. This pictorial review aims to provide an updated, image-rich overview of paediatric diffuse low-grade gliomas, emphasizing their typical and atypical imaging findings in MRI, offering valuable diagnostic insights for clinical practitioners and Radiologist.

Adenoid cystic carcinoma (ACC) with intracranial metastasis and sixth cranial nerve (CN VI) palsy, spinal metastases, and malignant spinal cord compression is an uncommon clinical entity. We present a case of a patient exhibiting this constellation of findings secondary to the parotid ACC. A 55-year-old man with no identifiable risk factors for ACC presented with a 10-year history of a left parotid tumor. He underwent two surgical resections and received one cycle of chemotherapy. Subsequently, his disease progressed locoregionally and systemically. He developed diplopia due to left sixth cranial nerve palsy caused by an intracranial metastatic lesion, together with complete spinal cord syndrome secondary to thoracic spinal metastases with malignant spinal cord compression. The patient was treated with whole-brain radiotherapy for intracranial metastasis and palliative spinal radiotherapy for spinal cord compression, achieving neurological stabilization without further deterioration. Systemic therapy with a tyrosine kinase inhibitor was subsequently initiated (lenvatinib 24 mg QD). The lungs are the most common site of distant metastasis in ACC, followed by bone and liver involvement. However, intracranial dissemination may occur rarely and should be considered in the clinical evaluation of these patients.

Diffuse midline glioma (DMG) is an aggressive malignancy driven by the H3K27M oncohistone, leading to global epigenetic dysregulation and limited efficacy of single-agent epigenetic therapies. We previously observed clinical benefit from an HDAC/EZH2 inhibitor-based therapeutic regimen, but the mechanistic basis was unclear. A panel of patient-derived DMG glioma stem cell (GSC) cultures from brainstem and spinal cord tumors was used for drug-response and functional assays, with representative models further analyzed for transcriptomic alterations, cell-cycle distribution, global histone-modification changes, self-renewal, and in vivo efficacy. Antitumor efficacy was validated in orthotopic xenografts. Panobinostat and tazemetostat showed robust synergy across patient-derived DMG GSC cultures, suppressing GSC growth, proliferation, and self-renewal while inducing apoptosis and G0/G1 cell-cycle arrest. Transcriptomic analyses revealed coordinated repression of cell-cycle programs and downregulation of OPC-like and stemness-associated programs, accompanied by the induction of differentiation-associated neuronal genes. Functionally, dual treatment reduced stem-cell frequency by >90% to >99%. In orthotopic xenografts, combination therapy significantly decreased tumor burden, reduced spinal dissemination, and prolonged survival. Together, these findings indicate that dual HDAC/EZH2 inhibition disrupts epigenetically maintained proliferative and stem-like programs through coordinated cell-cycle repression, apoptosis induction, and impaired self-renewal. This work supports HDAC/EZH2 co-targeting as a rational therapeutic backbone for H3K27-altered DMG and its incorporation into future rational combination strategies.

Early diagnosis of acute kidney injury (AKI) and identification of effective therapeutics remain significant clinical challenges. Herein, we developed an activatable near-infrared fluorescent nanoprobe (denoted PS-QRC) by encapsulating a self-amplifying fluorescent sensor (QRCy) within kidney-targetable L-serine-functionalized ultrasmall poly(amidoamine) (PAMAM-Ser) dendrimers. Upon activation by reactive oxygen species (ROS), QRCy undergoes self-fragmentation, releasing four fluorophores to amplify the fluorescence signal, affording an ultra-low detection limit of 81 nM for hydrogen peroxide. The L-serine modification enables specific binding of PS-QRC to kidney injury molecule-1 (KIM-1), which is overexpressed in injured renal tubules, thereby promoting renal accumulation and reducing background interference. Impressively, PS-QRC allows noninvasive real-time imaging of cisplatin-induced AKI in mice as early as 12 h, significantly earlier than conventional serum biochemical and histopathological analyses. Furthermore, a high-throughput screening platform was established using this nanoprobe to evaluate natural products, from which chrysin was identified as a promising renoprotective agent. Chrysin demonstrated both in vitro and in vivo renoprotective effects, with efficacy comparable to the established antioxidant N-acetylcysteine. Moreover, PS-QRC enabled quantitative monitoring of chrysin's dose-dependent therapeutic response. Overall, this integrated probe provides a sensitive and reliable tool for early AKI diagnosis and the high-throughput discovery of novel renoprotective drugs.

Neuropathic pain is a severe adverse complication of spinal cord injury (SCI) for which effective therapies are currently lacking. Resveratrol, a natural phytoalexin found in many plants and fruits, has been shown to relieve chemotherapy- and nerve injury-induced neuropathic pain and to promote functional recovery after SCI. In this study, we found that intraperitoneal administration of resveratrol increased the expression and activity of silent information regulator 1 (SIRT1) in the rat spinal dorsal horn and markedly attenuated neuropathic pain after SCI while improving motor recovery. Building on our previous finding that palmitoylation of δ-catenin promotes the membrane trafficking of the voltage-gated sodium channel Nav1.6 in dorsal root ganglion neurons and contributes to oxaliplatin- and nerve injury-induced neuropathic pain, we further examined whether resveratrol produces analgesia by inhibiting δ-catenin palmitoylation-mediated membrane accumulation of Nav1.6 in the spinal dorsal horn after SCI. Our results showed that SCI markedly increased both Nav1.6 membrane localization and δ-catenin palmitoylation in the dorsal horn and intrathecal delivery of Nav1.6 shRNA or pharmacological inhibition of palmitoylation with 2-bromopalmitate significantly attenuated mechanical allodynia after SCI. Resveratrol suppressed SCI-induced δ-catenin palmitoylation and reduced the pathological membrane accumulation of Nav1.6, an effect accompanied by downregulation of the palmitoyl acyltransferase ZDHHC3 (DHHC3). Together, these findings indicate that resveratrol alleviates neuropathic pain after SCI by inhibiting DHHC3-mediated δ-catenin palmitoylation and thereby suppressing the membrane trafficking of Nav1.6 in the spinal dorsal horn.

Dexpramipexole is a small molecule compound with properties previously shown to block the voltage-gated sodium channel, Nav1.8 on nociceptors. It additionally has anti-inflammatory properties in immune cells. In addition to clinical trials investigating the therapeutic efficacy of dexpramipexole to control eosinophilic asthma, dexpramipexole is effective in alleviating peripheral neuropathies in preclinical mouse models such as sciatic nerve chronic constriction injury, which reverses pathological sensitivity to light touch (i.e. allodynia). Pain signals are further processed in limbic areas of the brain that serve to regulate stress. Such overlapping regulation elicits increases in hypothalamic efferent sympathetic activity, which engages the spleen and adrenal glands in response to stress; organs critical in regulating immune responses and producing catecholaminergic norepinephrine, respectively. Thus, the current study evaluated the action of dexpramipexole (1) on the full timecourse of peripheral (intravenous) dexpramipexole and the acute timecourse of spinal (intrathecal) dexpramipexole on established allodynia from chronic constriction injury, and (2) characterized spinal and limbic proinflammatory cytokine protein expression following the spinal intrathecal dexpramipexole application in female mice. Splenic cytokine mRNA expression and adrenal norepinephrine levels were measured, as chronic constriction injury-induced neuropathy elicits elevated sympathetic nervous activity. Hindpaw sensitivity was assessed using the von Frey method. After intrathecal dexpramipexole and hindpaw reassessment at 1hr, the anterior cingulate cortex, amygdala, hypothalamus, dorsal lumbar spinal cord, lumbar dorsal root ganglia, spleen and adrenal glands were collected. Intravenous dexpramipexole, resulted in profound allodynic reversal within 1hr through 24hr, that returned by 48hr occurred. Intrathecal dexpramipexole, resulted in full reversal of allodynia by 1hr occurred. Chronic constriction injury-induced elevations in spinal interferon-γ protein was significantly suppressed from intrathecal dexpramipexole-treated mice that also demonstrated allodynia reversal, whereas trends for reduced spinal interleukin-1β and tumor necrosis factor-α were observed. Lumbar dorsal root ganglia from allodynic reversed mice given intrathecal dexpramipexole revealed reduced interleukin-1β and tumor necrosis factor-α, as was observed in the hypothalamus. Intrathecal dexpramipexole did not reliably alter splenic cytokine mRNA expression nor adrenal norepinephrine. These data suggest dexpramipexole may control allodynia by decreasing spinal interferon-γ and sensory ganglia interleukin-1β and tumor necrosis factor-α, which may serve as a potential pain therapeutic in addition to its action at Nav1.8.