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This article sets out key issues in determining and upholding the best interests of children, in need of social service support, who have family networks that span outside of the UK. These issues are then analysed against whether and how child protection professionals take these into account along with an overall consideration of the United Nations Convention on the Rights of the Child's (UNCRC) 'best interests of the child', when assessing and planning for those needs in kinship care cases. Building on these themes, the findings of an exploratory study on international kinship care cases carried out by Children and Families Across Borders (CFAB), the UK branch of the non-governmental organisation, International Social Service, as well as CFAB's associated Freedom of Information Requests to the UK government, are examined. These are then analysed in relation to legal and policy documents in England. Agency case records are analysed to identify a range of factors for children placed with 'kinship' carers across national borders, relating to the cultural relativity of the 'best interest' principle, the availability of family support in different social service structures, the understanding and application of legislation and policy in transnational contexts, and the availability of markers to track and analyse the scale of children crossing borders to join family.

Background: Metabolic stroke is the rapid onset of lasting central neurological deficit associated with decompensation of an underlying metabolic disorder. Glutaric aciduria type I (GA1) is an inherited disorder of lysine and tryptophan metabolism presenting with metabolic stroke in infancy. The clinical presentation includes bilateral striatal necrosis and spontaneous subdural and retinal hemorrhages, which has been frequently misdiagnosed as non-accidental head trauma. The mechanisms underlying metabolic stroke and spontaneous hemorrhage are poorly understood., Results: Using a mouse model of GA1, we show that metabolic stroke progresses in the opposite sequence of ischemic stroke, with initial neuronal swelling and vacuole formation leading to cerebral capillary occlusion. Focal regions of cortical followed by striatal capillaries are occluded with shunting to larger non-exchange vessels leading to early filling and dilation of deep cerebral veins. Blood-brain barrier breakdown was associated with displacement of tight-junction protein Occludin., Conclusion: Together the current findings illuminate the pathophysiology of metabolic stroke and vascular compromise in GA1, which may translate to other neurometabolic disorders presenting with stroke.

Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I.

Acute morphologic changes of brain due to chemically induced seizures are studied in developing rabbits. Accordingly, rabbits of postnatal days 6 and 7 (p6-7) and p10-12 are injected with a single dose of 1-6 mg/kg kainic acid (KA) intraperitoneally (i.p.) or injected with a single dose of 200-300 mg/kg pilocarpine subcutaneously (s.c.). Many animals developed seizures of varying severity and length. Histologic examination of brain 2 days following injection showed that KA-induced seizures did not cause neuronal death. Pilocarpine-induced seizures resulted in neuronal death mainly involving the CA1 region of hippocampus. In the p6-7 group, only a small number of brains were involved, lesions were mild and limited to CA1. In the p10-12 group, majority of the brains were damaged, lesions were relatively severe, and in some brains extended beyond the CA1 region involving the subiculum, CA3, cortex, and amygdala. Measurements of physiologic parameters indicate that these changes were not secondary to hypoxemia during seizures. However, there was hypotension and hyperthermia, both of which may contribute to brain damage during seizures. The findings suggest that pilocarpine-induced seizures during the second postnatal week in rabbits is a useful model to study the morphologic changes of brain due to seizure in the developing animal and also to assess the systemic physiologic alterations during seizures.

The present investigation was designed to study the effect of chemically induced seizures on cerebral hypoxic-ischemic (HI) damage in immature animals. Accordingly, cerebral HI was produced in 7-day postnatal (p7) rats and p13 rats by combined unilateral common carotid artery ligation and hypoxia with 8% oxygen. Seizures were induced chemically by the subcutaneous injection of kainic acid (KA) or inhalation of flurothyl vapor. Three types of experiments were conducted in each age group and for each convulsant. In some animals (group 1), seizures were produced at 24 h and again at 6 h prior to HI. In groups 2 and 3, seizures were induced 2 h or 24 h post HI, respectively. The results indicate that in group 1 animals, the first seizure significantly reduced duration of the second seizure challenge 18 h later at both p7 and p13 (p=0.001). Histologic examination of brains of animals in group 1 subjected to seizures prior to HI and their HI-only controls showed that seizures prior to HI conferred protection against cerebral damage. This effect was significant for flurothyl seizures in p13 rats for all cerebral regions, especially hippocampal CA1 (p=0.0004), and in p7 rats for hippocampus (p=0.04) and particularly cerebral cortex (p=0.007). For KA seizures, the protective effect was only significant in p13 rats and was limited to hippocampal CA regions and subiculum (p=0.0009). Histologic assessment of cerebral lesions of p7 and p13 rats in the other two groups showed no significant difference between the animals subjected to seizures 2 h or 24 h post HI and their HI-only controls (p>0.05). In conclusion, the results of the present study provide no evidence that seizures in early postnatal development aggravate pre-existing cerebral HI damage. They do suggest that seizures prior to HI or prior to a second seizure confer tolerance to both conditions., (Copyright 1999 Elsevier Science B.V.)

Neutrophils contribute to ischemic brain injury in adult animals. The role of neutrophils in perinatal hypoxic-ischemic (HI) brain injury is unknown. Allopurinol reduces neutrophil accumulation after tissue ischemia and is protective against HI brain injury. This study was designed to investigate how neutrophils contribute to perinatal hypoxic ischemic brain injury and how neutropenia compared with allopurinol in its neuroprotective effects. A HI insult was produced in the right cerebral hemisphere of 7-d-old rats by right common carotid artery ligation and systemic hypoxia. Half the rats were rendered neutropenic with an anti-neutrophil serum (ANS). At 15 min of recovery from hypoxia, half the neutropenic and nonneutropenic rats received allopurinol (135 mg/kg, s.c.). The protective effect of the four treatment combinations was determined on brain swelling at 42 h of recovery. Neutropenia reduced brain swelling by about 70%, p < 0.01. Allopurinol alone produced similar protection so that the relatively small number of animals studied did not permit assessment of an additive effect. Neutrophil accumulation in cerebral hemispheres was measured by myeloperoxidase (MPO) activity assay and by neutrophil counts in 6-microm sections stained by MPO and ANS immunostaining. MPO activity peaked between 4 and 8 h of recovery in both hemispheres. Hemispheric neutrophil counts peaked at the end of the HI insult and again at 18 h of recovery. Neutrophils were stained within blood vessels and did not infiltrate the injured brain before infarction had occurred. We conclude that neutrophils contribute to HI brain injury in the neonate and that neutrophil depletion before the insult is neuroprotective.

The sequential evolution of neuropathologic changes was studied in an immature model of cerebral hypoxia-ischemia. According, 7-day postnatal rats were subjected to unilateral common carotid artery ligation combined with 2 h of hypoxia (breathing in 8% oxygen) and their brains were examined by light microscopy at recovery intervals ranging from 0 to 3 weeks. Immediately following hypoxia, a large area with a pale staining border was noted occupying most of the cerebral hemisphere ipsilateral (IL) to the occluded common carotid artery; in approximately half of the brains the dorsomedial cortex of the contralateral (CL) hemisphere was also involved. Most neurons in the pale area had nuclei containing a coarse granular condensation of chromatin. Within a few hours, the majority of neurons in the IL hemisphere had developed pyknotic nuclei and clear or eosinophilic perikarya. After 24 h these changes had evolved in the majority of brains into coagulation necrosis (infarction) in the IL hemisphere and foci of selective neuronal necrosis in the CL cortex. Within a few days infarcts became partially cavitated, and by 3 weeks a smooth-walled cystic infarct had developed. Activated microglia/macrophages and reactive astrocytes were first seen at 4 and 24 h, respectively. No parenchymal neutrophilic infiltrate was seen at any time point.

The effect of unilateral perinatal cerebral hypoxic-ischemic damage on the gross development of the opposite hemisphere was investigated in immature rats. Eight-day-old rats underwent unilateral common carotid artery ligation followed by exposure to hypoxia (8% oxygen) ranging from 1 to 2 h at 37 degrees C. The animals were sacrificed 3 weeks later, and brain damage was assessed histologically, by weighing the cerebral hemispheres, and by measuring hemispheric cross-sectional area and diameter as well as the thickness of neocortex. There were no significant differences in either the size or cortical thickness of the cerebral hemisphere contralateral to the damaged hemisphere compared to those of controls. The results are comparable to the effect of unilateral perinatal hemispheric decortication and hemispherectomy on the growth of the contralateral hemisphere and suggest that: (1) perinatal damage to one cerebral hemisphere does not significantly alter the size of the other hemisphere, and (2) the contralateral hemisphere may be used as a 'normal' reference in evaluating the extent of atrophy or infarction of a cerebral hemisphere damaged earlier by perinatal hypoxia-ischemia.

We compared the efficacy of four different classes of anesthetics to arrest the progression of brain damage after chemoconvulsant-induced seizures in rats. In two series of experiments, ventilated, paralyzed Long-Evans rats were subjected to 30 or 45 min of continuous seizures induced by intravenous (IV) mercaptopropionic acid (MPA) or inhaled flurothyl, respectively. In the first series, seizures produced with MPA were treated with: 1) thiopental, 15 mg/kg IV bolus (controls); 2) thiopental, 27 mg/kg IV followed by 20.9 mg.kg-1.h-1 for 2 h; 3) isoflurane 4% inhaled concentration for 1 min followed by 1%-2% for 2 h; 4) ketamine 30 mg/kg IV followed by 9.12 mg.kg-1.h-1 for 2 h; 5) midazolam 25 mg/kg IV followed by 9.7 mg.kg-1.h-1 for 2 h. In a second series, seizures were produced by flurothyl and, based on suggestive results in the MPA series, control rats were compared with rats receiving midazolam 25 mg/kg IV followed by 9.7 mg.kg-1.h-1. In all instances, seizure activity, recorded by electroencephalograph, stopped with anesthetic treatment. In MPA-treated rats extranigral damage was mild, with no differences apparent between anesthetics. Control animals sustained severe lesions in the substantia nigra pars reticulata (SNPR). No statistically significant differences between anesthetic groups were present, although an effect was suggested for midazolam to decrease SNPR lesional area (P = 0.06). In flurothyl-treated rats, there were significant reductions in SNPR neuropathologic grade (P = 0.025) and lesional area (P = 0.025) with midazolam. We conclude that midazolam attenuates postseizure SNPR damage in rats.