Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice.

Reactive astrocytes adjacent to a forebrain stab injury were selectively ablated in adult mice expressing HSV-TK from the Gfap promoter by treatment with ganciclovir. Injured tissue that was depleted of GFAP-positive astrocytes exhibited (1) a prolonged 25-fold increase in infiltration of CD45-positive leukocytes, including ultrastructurally identified monocytes, macrophages, neutrophils, and lymphocytes, (2) failure of blood-brain barrier (BBB) repair, (3) substantial neuronal degeneration that could be attenuated by chronic glutamate receptor blockade, and (4) a pronounced increase in local neurite outgrowth. These findings show that genetic targeting can be used to ablate scar-forming astrocytes and demonstrate roles for astrocytes in regulating leukocyte trafficking, repairing the BBB, protecting neurons, and restricting nerve fiber growth after injury in the adult central nervous system.

Hippocampal neurotrophin and trk receptor mRNA levels are altered by local administration of nicotine, carbachol and pilocarpine.

Cholinergic receptor agonists nicotine (nicotinic), carbachol (nicotinic/muscarinic) and pilocarpine (muscarinic) were administered into the hippocampus and mRNA levels of neurotrophins and their receptors determined using in situ hybridisation. Drug doses were carefully chosen to avoid the potentially confounding effects of seizure and cell death. Nicotine caused a long-lasting increase in nerve growth factor (NGF) mRNA in all subfields of the hippocampus. The increase was evident from 24 h up to 72 h after drug administration. This increase was dependent on excitatory amino acid neurotransmission as it was blocked by administration of an AMPA or NMDA receptor antagonist. In contrast, carbachol and pilocarpine produced a transient increase in NGF mRNA levels present 4-8 h after drug administration. Pilocarpine caused a transient increase in hippocampal brain-derived neurotrophic factor (BDNF) levels, with carbachol and nicotine showing the same trend. Nicotine and carbachol caused transient decreases in NT-3 mRNA levels in dentate gyrus and CA2 with pilocarpine showing a similar trend. Increases in mRNA encoding full-length trkB were seen 8 h after nicotine, with nicotine also causing elevations in a mRNA encoding a truncated isoform (trkB.T2). TrkC mRNA was not altered by any of the conditions used. The study suggests that muscarinic and nicotinic receptor activation in the hippocampus causes transient changes in all of the neurotrophins, but that NGF levels are selectively up-regulated by nicotinic receptor stimulation. The reciprocal interaction between NGF and ascending cholinergic systems may be a component of the cognitive enhancing effects of nicotine.

Reduction in numerical synapse density in chick (Gallus domesticus) dorsal hippocampus following transient cerebral ischaemia.

Transient forebrain ischaemia was induced by a two-vessel occlusion method in the domestic chick. One week post-surgery, hippocampal tissue was processed for electron microscopy and synapse density assessed using the disector technique. Hippocampal volume was estimated using image analysis of serial coronal cryostat sections. The density of asymmetric synapses was significantly reduced (27%; P < 0.005) in ischaemic chicks. This appears to be a real reduction as hippocampal volume was not significantly decreased.

Reduction in numerical synapse density in chick (Gallus domesticus) dorsal hippocampus following transient cerebral ischaemia.

Transient forebrain ischaemia was induced by a two-vessel occlusion method in the domestic chick. One week post-surgery, hippocampal tissue was processed for electron microscopy and synapse density assessed using the disector technique. Hippocampal volume was estimated using image analysis of serial coronal cryostat sections. The density of asymmetric synapses was significantly reduced (27%; P < 0.005) in ischaemic chicks. This appears to be a real reduction as hippocampal volume was not significantly decreased.

A quantitative study of the perikaryon and the basal dendritic tree in rat hippocampus (CA1) pyramids following different experimental procedures.

A quantitative study of perikaryon and basal dendritic branching of hippocampal (CA1) neurons in male Wistar rats, in three experimental groups is reported. The groups of animals were exposed to treatment with either a tricyclic antidepressant, or a saline control injection or no handling. The hippocampal tissue was studied following Golgi-Kopsch impregnation and comparative measurements made using semi-automatic image analysis and light microscopy. Measurements of the extent of basal dendritic branching showed a significant difference (p < 0.01) between the saline-injected and unhandled control groups. The drug-injected and saline-injected groups had similar values although the drug-injected group did not prove to be significantly different from the unhandled controls. No statistical difference was noted in the perikaryon size of the three experimental groups. These results are discussed with reference to the effects of sensory stimulation on neuronal plasticity.

Methods of estimation of spine density--are spines evenly distributed throughout the dendritic field?

Dendritic spines are small protrusions extending from the dendrites of nerve cells, which bear the majority of synapses. In the past, researchers quantified spine density as the number of visible spines per estimated micrometre of dendrite. This estimate ignores all those spines hidden from view due to their position on the dendrite. Dendrites vary in diameter and the underestimation in some will be greater than others. Estimation of dendritic length is also subjective and difficult in those which are tortuous. The Felman & Peters (1979) geometrical equation takes account of these criteria and provides a method of estimating 'true' spine numbers which does not involve slow and laborious reconstruction. This study compares ratios derived from both methods of estimation (spine density 2:1) at three loci in three experimental groups. Mean values of dendritic diameters and spine dimensions show the major cause for variation in the ratios between loci to be the shaft diameter of the dendrite. However, the greater ratio for apical as compared with basal and oblique dendrites is not as great as expected, bearing in mind that apical dendrites are approximately 2.5 times larger than oblique and basal dendrites. Therefore the spine distribution may not be the same throughout the dendritic field. Estimations of spine density based on visible spine counts are quicker, easier and sufficient for comparisons within the same locus. 'True' estimates (spine density 2) are more accurate and should be used when comparisons are being made between loci, cell types and species.

Neural plasticity of the hippocampal (CA1) pyramidal cell--quantitative changes in spine density following handling and injection for drug testing.

A quantitative assessment of the spine density of apical, basal and oblique dendrites on pyramidal neurons of area CA1 of the hippocampus was made in three experimental groups. The results of a group injected with a tricyclic antidepressant were compared statistically with a saline-injected group and an unhandled control group. A statistical analysis of variance indicated significant (P less than 0.01) differences between drug and control groups and between saline and control groups in two of the loci assessed (basal and oblique dendrites). These findings suggest that the sensory stimulation provided by daily injection and handling is responsible for the increases in spine density in drug- and saline-injected animals. A single control group is insufficient in experiments of this type. Experimental protocol is extremely important and the dramatic morphological changes produced by simple routine processes should not be under-estimated.

Hippocampal synaptic density and glutamate immunoreactivity following transient cerebral ischaemia in the chick.

A transient ischaemic episode of 10 min duration was induced in 1-day-old chicks. After a 1-week survival period, synapse density was assessed in the ventral hippocampus using the 'disector' technique. A significant decrease was observed in asymmetric synapses, markedly greater than that observed previously in the dorsal hippocampus. Because the effect occurred mainly on excitatory synapses, the distribution of glutamate in the ventral hippocampus was also assessed by a postembedding immunogold labelling technique. The density of gold particles was significantly greater in both boutons and neuropil in the ischaemic group compared to controls, lending support to the theory of excitotoxicity as an explanation for ischaemic neural degeneration.

Motorcycle racing injuries on track and road circuits in Ireland.

A retrospective study was carried out on all motorcycle injuries occurring at Mondelo Park racetrack for the 1983 and 1984 seasons. In this sport there were a total of 57 injuries for the two year period, 27 occurring in 1983 and 30 in 1984. Soft tissue injuries accounted for 66.7%, fractures 22.8% and head injuries 10.5% of the total. In the fracture group, 2 patients suffered spinal fractures which is noteworthy in that neither were wearing back protectors which as yet are not compulsory safety equipment in Eire. These figures were compared with data from the same two year period on the Ulster road circuit. The incidence of each type of injury was similar and equally low in both groups. Motorcycle racing injuries compared favourably with motor car racing injuries and had a lower incidence of serious head injury. In comparison with road traffic accidents involving motorcyclists the overall number of injuries, the number of serious head, abdominal and chest injuries and the overall fatality rate, are much lower. The two most relevant factors in our lower injury incidence were lack of alcohol and the absence of collision with cars. Experience, medical attention and speed had no direct influence on our injury incidence.