Higher n-3 Polyunsaturated Fatty Acid Diet Improves Long-Term Neuropathological and Functional Outcome after Repeated Mild Traumatic Brain Injury.

Repeated mild traumatic brain injury (TBI) can cause persistent neuropathological effects and is a major risk factor for chronic traumatic encephalopathy. PUFAs (n-3 polyunsaturated fatty acids) were shown to improve acute TBI outcomes in single-injury models in most cases. In this study, we demonstrate positive effects of dietary n-3 PUFA on long-term neuropathological and functional outcome in a clinically relevant model of repeated mild TBI using the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA). Adult mice, reared on n-3 PUFA adequate (higher n-3 PUFA) or deficient (lower n-3 PUFA) diets, were given a mild CHIMERA daily for 3 consecutive days. At 2 months after injury, visual function and spatial memory were evaluated. Glia cell activation was assessed by immunostaining using antibodies of ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein, and axonal damage was examined using silver staining. Repeated CHIMERA (rCHIMERA)-induced gliosis was significantly suppressed in the optic tract, corpus callosum, and hippocampus of mice fed the n-3 PUFA adequate diet compared to the deficient diet group. Considerable axonal damage was detected in the optic tract after rCHIMERA, but the adequate diet group displayed less axonal damage compared to the deficient diet group. rCHIMERA induced a drastic reduction in N1 amplitude of the visual evoked potential in both diet groups and the a-wave amplitude of the electroretinogram in the deficient diet group. However, reduction of N1 and a-wave amplitude were less severe in the adequate diet group. The Morris water maze probe test indicated a significant decrease in the number of platform crossings in the deficient diet group compared to the adequate group. In summary, dietary n-3 PUFA can attenuate persistent glial cell activation and axonal damage and improve deficits in visual function and spatial memory after repeated mild TBI. These data support the neuroprotective potential of a higher n-3 PUFA diet in ameliorating the adverse outcome of repeated mild TBI.

Investigation of the effect of dietary intake of omega-3 polyunsaturated fatty acids on trauma-induced white matter injury with quantitative diffusion MRI in mice.

Previous studies suggest that long-term supplementation and dietary intake of omega-3 polyunsaturated fatty acids (PUFAs) may have neuroprotective effects following brain injury. The objective of this study was to investigate potential neuroprotective effects of omega-3 PUFAs on white matter following closed-head trauma. The closed-head injury model of engineered rotational acceleration (CHIMERA) produces a reproducible injury in the optic tract and brachium of the superior colliculus in mice. Damage is detectable using diffusion tensor imaging (DTI) metrics, particularly fractional anisotropy (FA), with sensitivity comparable to histology. We acquired in vivo (n = 38) and ex vivo (n = 41) DTI data in mice divided into sham and CHIMERA groups with two dietary groups: one deficient in omega-3 PUFAs and one adequate in omega-3 PUFAs. We examined injury effects (reduction in FA) and neuroprotection (FA reduction modulated by diet) in the optic tract and brachium. We verified that diet did not affect FA in sham animals. In injured animals, we found significantly reduced FA in the optic tract and brachium (~10% reduction, p < 0.001), and Bayes factor analysis showed strong evidence to reject the null hypothesis. However, Bayes factor analysis showed substantial evidence to accept the null hypothesis of no diet-related FA differences in injured animals in the in vivo and ex vivo samples. Our results indicate no neuroprotective effect from adequate dietary omega-3 PUFA intake on white matter damage following traumatic brain injury. Since damage from CHIMERA mainly affects white matter, our results do not necessarily contradict previous findings showing omega-3 PUFA-mediated neuroprotection in gray matter.

Refinement of Spatial Receptive Fields in the Developing Mouse Lateral Geniculate Nucleus Is Coordinated with Excitatory and Inhibitory Remodeling.

Receptive field properties of individual visual neurons are dictated by the precise patterns of synaptic connections they receive, including the arrangement of inputs in visual space and features such as polarity (On vs Off). The inputs from the retina to the lateral geniculate nucleus (LGN) in the mouse undergo significant refinement during development. However, it is unknown how this refinement corresponds to the establishment of functional visual response properties. Here we conducted in vivo and in vitro recordings in the mouse LGN, beginning just after natural eye opening, to determine how receptive fields develop as excitatory and feedforward inhibitory retinal afferents refine. Experiments used both male and female subjects. For in vivo assessment of receptive fields, we performed multisite extracellular recordings in awake mice. Spatial receptive fields at eye-opening were >2 times larger than in adulthood, and decreased in size over the subsequent week. This topographic refinement was accompanied by other spatial changes, such as a decrease in spot size preference and an increase in surround suppression. Notably, the degree of specificity in terms of On/Off and sustained/transient responses appeared to be established already at eye opening and did not change. We performed in vitro recordings of the synaptic responses evoked by optic tract stimulation across the same time period. These recordings revealed a pairing of decreased excitatory and increased feedforward inhibitory convergence, providing a potential mechanism to explain the spatial receptive field refinement.SIGNIFICANCE STATEMENT The development of precise patterns of retinogeniculate connectivity has been a powerful model system for understanding the mechanisms underlying the activity-dependent refinement of sensory systems. Here we link the maturation of spatial receptive field properties in the lateral geniculate nucleus (LGN) to the remodeling of retinal and inhibitory feedforward convergence onto LGN neurons. These findings should thus provide a starting point for testing the cell type-specific plasticity mechanisms that lead to refinement of different excitatory and inhibitory inputs, and for determining the effect of these mechanisms on the establishment of mature receptive fields in the LGN.

Pediatric Optic Pathway/Hypothalamic Glioma.

Optic pathway/hypothalamic gliomas (OP/HGs) are rare astrocytic tumors that appear more commonly among young children and often are unresectable. They comprise approximately 2% of all central nervous system tumors and account for 3-5% of pediatric intracranial tumors. Initial manifestations are often visual disturbances, endocrinopathies and hypothalamic dysfunction such as the diencephalic syndrome, and sometimes hydrocephalus due to cerebrospinal fluid (CSF) outflow obstruction. In many cases, the tumors are diagnosed late in the clinical course because they silently enlarge. These tumors consist mostly of histologically benign, World Health Organization (WHO) grade I tumors represented by pilocytic astrocytomas (PA), the rest being pilomyxoid astrocytomas (PXA) - WHO grade II tumors. In young pediatric patients, however, can be seen PXA that show aggressive clinical course such as CSF dissemination. Our small series of 14 non-Neurofibromatosis type 1 (NF-1) OP/HGs PA patients underwent extended resection without any adjuvant treatments. The median age at initial treatment was 11.5 ± 6.90 years (range, 1-25 years) and median follow up 85.5 ± 25.0 months. Surgical resection for OP/HGs results in acceptable middle-term survival, tumor control and functional outcome equivalent to chemotherapy. There is, however, no longer doubt that chemotherapy with or without biopsy and as-needed debulking surgery remains the golden standard in management of OP/H. Clinical conditions and treatment plans for OP/HGs vary depending on their structure of origin.

Pediatric Glioma at the Optic Pathway and Thalamus

Gliomas are the most common pediatric tumors of the central nervous system. In this review, we discuss the clinical features, treatment paradigms, and evolving concepts related to two types of pediatric gliomas affecting two main locations: the optic pathway and thalamus. In particular, we discuss recently revised pathologic classification, which adopting molecular parameter. We believe that our review contribute to the readers' better understanding of pediatric glioma because pediatric glioma differs in many ways from adult glioma according to the newest advances in molecular characterization of this tumor. A better understanding of current and evolving issues in pediatric glioma is needed to ensure effective management decision.

Pediatric Glioma at the Optic Pathway and Thalamus

Gliomas are the most common pediatric tumors of the central nervous system. In this review, we discuss the clinical features, treatment paradigms, and evolving concepts related to two types of pediatric gliomas affecting two main locations: the optic pathway and thalamus. In particular, we discuss recently revised pathologic classification, which adopting molecular parameter. We believe that our review contribute to the readers' better understanding of pediatric glioma because pediatric glioma differs in many ways from adult glioma according to the newest advances in molecular characterization of this tumor. A better understanding of current and evolving issues in pediatric glioma is needed to ensure effective management decision.

Intraoperative Subcortical Electrical Mapping of the Optic Tract in Awake Surgery Using a Virtual Reality Headset.

BACKGROUND: Brain mapping during awake craniotomy is a well-known technique to preserve neurological functions, especially the language. It is still challenging to map the optic radiations due to the difficulty to test the visual field intraoperatively. To assess the visual field during awake craniotomy, we developed the Functions' Explorer based on a virtual reality headset (FEX-VRH). METHODS: The impaired visual field of 10 patients was tested with automated perimetry (the gold standard examination) and the FEX-VRH. The proof-of-concept test was done during the surgery performed on a patient who was blind in his right eye and presenting with a left parietotemporal glioblastoma. The FEX-VRH was used intraoperatively, simultaneously with direct subcortical electrostimulation, allowing identification and preservation of the optic radiations. RESULTS: The FEX-VRH detected 9 of the 10 visual field defects found by automated perimetry. The patient who underwent an awake craniotomy with intraoperative mapping of the optic tract using the FEX-VRH had no permanent postoperative visual field defect. CONCLUSION: Intraoperative visual field assessment with the FEX-VRH during direct subcortical electrostimulation is a promising approach to mapping the optical radiations and preventing a permanent visual field defect during awake surgery for epilepsy or tumor.