Cerebral Palsy

Eeffects of perfluorooctane sulfonate (PFOS) on maleic dialdehyde (MDA) content, superoxide dismutase (SOD) activity and total antioxidation capability (T-AOC) were compared in mice at different postnatal developmental stages, and concentrations and distributions of PFOS in different tissues were measured simultaneously. The male and female mice at postnatal day (PD) 7, PD 14, PD 21, PD 28 and PD 35 were distributed randomly to dosage group (50 mg/kg body weight) and control group (0 mg/kg body weight). Mice were administered with PFOS by once subcutaneous injection. Subsequently, after 24 hr, MDA content, SOD activity and T-AOC in brain and liver were analyzed. The PFOS concentrations in blood, brain and liver were determined by high-performance liquid chromatography negative electrospray tandem mass spectrometry (LC-MS). PFOS induced degression of the body weights of mice evidently and increase of relative weights of liver. Meanwhile, it depressed the SOD activity and T-AOC in brain and liver. The concentrations and distribution percentages of PFOS in blood, brain and liver of mice were significantly different at various postnatal developmental stages. Achieved results in this study indicate that younger mice pups were more sensitive to PFOS exposure. In addition, significant distinctions in concentrations and distribution percentages of PFOS in various tissues were demonstrated in this study. The gender difference observed was greater in the older mice. Thus it is worth giving attention especially to adverse effects of PFOS on foetus and children.

Fractures of the odontoid in children with an open basilar synchondrosis differ from those which occur in older children and adults. We have reviewed the morphology of these fractures and present a classification system for them. There were four distinct patterns of fracture (types IA to IC and type II) which were distinguished by the site of the fracture, the degree of displacement and the presence or absence of atlantoaxial dislocation. Children with a closed synchondrosis were classified using the system devised by Anderson and D’Alonzo. Those with an open synchondrosis had a comparatively lower incidence of traumatic brain injury, a higher rate of missed diagnosis and a shorter mean stay in hospital. Certain subtypes (type IA and type II) are likely to be missed on plain radiographs and therefore more advanced imaging is recommended. We suggest staged treatment with initial stabilisation in a Halo body jacket and early fusion for those with unstable injuries, severe displacement or neurological involvement.

Administration of the neurosteroid progesterone (PROG) has been shown to be beneficial in a number of brain injury models and in two recent clinical trials. Given widespread vitamin D deficiency and increasing traumatic brain injuries (TBIs) in the elderly, we investigated the interaction of vitamin D deficiency and PROG with cortical contusion injury in aged rats. Vitamin D deficient (VitD-deficient) animals showed elevated inflammatory proteins (TNFalpha, IL-1beta, IL-6, NFkappaB p65) in the brain even without injury. VitD-deficient rats with TBI, whether given PROG or vehicle, showed increased inflammation and greater open-field behavioral deficits compared to VitD-normal animals. Although PROG was beneficial in injured VitD-normal animals, in VitD-deficient subjects neurosteroid treatment conferred no improvement over vehicle. A supplemental dose of 1,25-dihydroxyvitamin D(3) (VDH) given with the first PROG treatment dramatically improved results in VitD-deficient rats, but treatment with VDH alone did not. Our results suggest that VitD-deficiency can increase baseline brain inflammation, exacerbate the effects of TBI, and attenuate the benefits of PROG treatment; these effects may be reversed if the deficiency is corrected.

OBJECTIVE: To describe cases of severe child abuse admitted to PICU. METHODS AND PATIENTS: It is a retrospective study (2000-2008) in which patients diagnosed with physical child abuse admitted to PICU were included. Other abuse patterns were excluded (severe negligence, sexual abuse or scalding). RESULTS: There were 8 patients included (3 boys and 5 girls). The median age was 5.2 months, with 6 patients were less than 7 months old. The most frequent sign was neurological symptoms: seizures (4 patients), subdural haematoma (2 patients), traumatic brain injury (1 patient). Other: haemothorax (1 patient) and cardiac arrest of no known aetiology (1 patient). The CT showed a subdural haematoma in 5 patients, 3 of which needed surgical drainage. Child abuse was confirmed using the social history and the presence of inflicted injuries. There were long bones fractures (tibia, ulna and radius, bilateral rib fractures) in 3 patients and 4 patients had retinal haemorrhages. There was one death and 3 had severe neurological after effects. CONCLUSION: Severely abused children can be falsely diagnosed with a casual neurological disease. The most frequent injury is subdural haematoma with or without another injury associated to child abuse. It very important to diagnose child abuse in order to prevent recurrent injuries.

Recently we reported that declined SQSTM1/p62 expression in Alzheimer disease brain was age-correlated with oxidative damage to the p62 promoter. The objective of this study was to examine whether oxidative damage to the p62 promoter is common to DNA recovered from brain of individuals with neurodegenerative disease. Increased 8-OHdG staining was observed in brain sections from Alzheimer’s disease (AD), Parkinson disease (PD), Huntington disease (HD), Frontotemporal dementia (FTD), and Pick’s disease compared to control subjects. In parallel, the p62 promoter exhibited elevated oxidative damage in samples from various diseases compared to normal brain, and damage was negatively correlated with p62 expression in FTD samples. Oxidative damage to the p62 promoter induced by H(2)O(2) treatment decreased its transcriptional activity. In keeping with this observation, the transcriptional activity of a Sp-1 element deletion mutant displayed reduced stimulus-induced activity. These findings reveal that oxidative damage to the p62 promoter decreased its transcriptional activity and might therefore account for decreased expression of p62. Altogether these results suggest that pharmacological means to increase p62 expression may be beneficial in delaying the onset of neurodegeneration.

Previous scientific research has elucidated the correlation between changes in levels of the DNA base excision repair protein, apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1), and ischemic neuronal DNA damage. However, to date, no studies have addressed the question of whether treatment involving this protein’s repair function may prevent ischemic neuron death in vivo. Therefore, we aimed to investigate whether treatment with APE peptide is sufficient to prevent neuron death after ischemia/reperfusion (I/R) in mice. Mice were subjected to intraluminal suture occlusion of the middle cerebral artery for 1 hour followed by reperfusion. Post-ischemic treatment with the peptide containing only the APE repair functional domain was introduced intracerebroventricularly. Endonuclease activity assay and immunohistochemistry were performed. Assays of apurinic/apyrimidinic (AP) sites, single-strand DNA breaks, caspase-3 activity, and cell death were examined and quantified. We found that post-ischemic administration of the APE peptide up to 4hours after reperfusion significantly inhibited the induction of cell death and subsequent infarct volume, measured 24hours after I/R.

SMND-309, a novel compound named (2E)-2-{6-[(E)-2-carboxylvinyl]-2,3-dihydroxyphenyl}-3-(3,4-dihydroxyphenyl) propenoic acid, is a new derivate of salvianolic acid B. The present study was conducted to investigate whether SMND-309 has a protective effect on brain injury after focal cerebral ischemia, and if it did so, to investigate its effects on brain mitochondria. Adult male SD rats were subjected to middle cerebral artery occlusion (MCAO) by bipolar electro-coagulation. Behavioral tests and brain patho-physiological tests were used to evaluate the damage to central nervous system. Origin targets including mitochondria production of reactive oxygen species, antioxidant potentia, membrane potential, energy metabolism, mitochondrial respiratory enzymes activities and mitochondria swelling degree were evaluated. The results showed that SMND-309 decreased neurological deficit scores, reduced the number of dead hippocampal neuronal cells in accordance with its depression on mitochondria swelling degree, reactive oxygen species production, improvements on mitochondria swelling, energy metabolism, membrane potential level and mitochondrial respiratory chain complex activities. All of these findings indicate that SMND-309 exerted potent neuroprotective effects in the model of permanent cerebral ischemia, contributed to its protections on brain mitochondrial structure and function.

Brain-derived neurotrophic factor (BDNF) plays a regulatory role in neuronal differentiation and synaptic plasticity and has been linked to glucose regulation and cognition. Associations among plasma BDNF, cognition, and insulin function were explored. Forty-one participants with impaired insulin function (IIF), ranging from insulin resistance to type 2 diabetes mellitus (T2DM), were matched with 41 healthy controls on gender, age, education, and IQ. Participants received complete medical, neurological, psychiatric, and neuropsychological evaluations. IIF individuals had significantly lower plasma BDNF levels than controls, particularly females, and higher BDNF levels were associated with poorer explicit memory in IIF females, suggesting that higher levels within this group may reflect the body’s efforts to respond to damage. After accounting for age, education, and HbA1c, BDNF significantly predicted 13.1-23.5% of the variance in explicit memory in IIF women. These findings suggest that BDNF elevations within diseased groups may not always be a marker of health.

Following severe traumatic brain injury (TBI), a complex interplay of pathomechanism, such as exitotoxicity, oxidative stress, inflammatory events, and mitochondrial dysfunction occur. This leads to a cascade of neuronal and axonal pathologies, which ultimately lead to axonal failure, neuronal energy metabolic failure, and neuronal death, which in turn determines patient outcome. For mild and moderate TBI, the pathomechanism are similar but much less frequent and ischemic cell death is unusual, except with mass lesions. Involvement of mitochondria in acute post-traumatic neurodegeneration has been extensively studied during the last decade, and there are a number of investigations implicating the activation of the mitochondrial permeability transition pore (mPTP) as a “critical switch” which determines cell survival after TBI. Opening of the mPTP is modulated by several factors occurring after a severe brain injury. Modern neuroprotective strategies for prevention of the neuropathological squeal of traumatic brain injury have now begun to address the issue of mitochondrial dysfunction, and drugs that protect mitochondrial viability and prevent apoptotic cascade induced by mPTP opening are about to begin phase II and III clinical trials. Cyclosporin A, which has been reported to block the opening of mPTP, showed a significant decrease in mitochondrial damage and intra-axonal cytoskeletal destruction thereby protecting the axonal shaft and blunting axotomy. This review addresses an important issue of MPT activation after severe head injury, its role in acute post-traumatic neurodegeneration, and the rationale for targeting the mPTP in experimental and clinical TBI studies.

PURPOSE: In this article, we investigate the role of tumor necrosis factor-alpha (TNF) in the initiation of acute damage to the blood-brain barrier (BBB) and brain tissue following radiotherapy (RT) for CNS tumors. METHODS AND MATERIALS: Intravital microscopy and a closed cranial window technique were used to measure quantitatively BBB permeability to FITC-dextran 4.4-kDa molecules, leukocyte adhesion (Rhodamine-6G) and vessel diameters before and after 20-Gy cranial radiation with and without treatment with anti-TNF. Immunohistochemistry was used to quantify astrogliosis post-RT and immunofluorescence was used to visualize protein expression of TNF and ICAM-1 post-RT. Recombinant TNF (rTNF) was used to elucidate the role of TNF in leukocyte adhesion and vessel diameter. RESULTS: Mice treated with anti-TNF showed significantly lower permeability and leukocyte adhesion at 24 and 48 h post-RT vs. RT-only animals. We observed a significant decrease in arteriole diameters at 48 h post-RT that was inhibited in TNF-treated animals. We also saw a significant increase in activated astrocytes following RT that was significantly lower in the anti-TNF-treated group. In addition, immunofluorescence showed protein expression of TNF and ICAM-1 in the cerebral cortex that was inhibited with anti-TNF treatment. Finally, administration of rTNF induced a decrease in arteriole diameter and a significant increase in leukocyte adhesion in venules and arterioles. CONCLUSIONS: TNF plays a significant role in acute changes in BBB permeability, leukocyte adhesion, arteriole diameter, and astrocyte activation following cranial radiation. Treatment with anti-TNF protects the brain’s microvascular network from the acute damage following RT.