Peripheral changes above and below injury level lead to prolonged vascular responses following high spinal cord injury.

Autonomic dysreflexia (AD) is a debilitating disorder producing episodes of extreme hypertension in patients with high-level spinal cord injury (SCI). Factors leading to AD include loss of vasomotor baroreflex control to regions below injury level, changes in spinal circuitry, and peripheral changes. The present study tested for peripheral changes below and above injury level 6 wk after a transection at the fourth thoracic spinal level. Changes in vascular conductance were recorded in the femoral, renal, brachial, and carotid arteries in response to intravenous injections of two alpha-adrenergic agonists, phenylephrine (PE; 0.03-100 microg/kg) and methoxamine (Meth; 1-300 microg/kg). Unlike PE, Meth is not subject to neuronal reuptake. Ganglionic blockade (0.6 mg/kg chlorisondamine) was used to eliminate the central component of the cardiovascular response. After ganglionic blockade, SCI animals exhibited prolonged vasoconstriction in response to PE in all blood vessels measured compared with those in intact animals (all, P < 0.035). However, the PE dose-response curves obtained after ganglionic blockade revealed no significant difference in the potency between the two groups (all, P > 0.06), indicating that the prolonged vasoconstriction was not due to supersensitivity to PE. In contrast to PE, vascular responses to Meth did not vary between intact and SCI groups (all P > 0.108). These results show the development of a widespread peripheral change producing prolonged vasoconstriction in response to PE, but not Meth, possibly due to reduced neuronal reuptake of PE after SCI. This is the first study to report such a change in blood vessels not only below but also above injury level. Interventions to correct this reduced reuptake may help limit the development of AD.

Mild neuritic changes are increased in the brains of fatally injured older motor vehicle drivers.

Given the expected increase in the older population and driving in this age group, concerns have been raised about the safety of older drivers. People over 65 years are over-represented in motor vehicle fatalities when calculated by distance driven. They are also at risk of neurodegenerative diseases, such as Alzheimer's disease, that affect cognitive function. We have examined the brains of older drivers (15M:12F) who died as a result of a motor vehicle accident (MVA) to determine the extent of Alzheimer's disease-related neurofibrillary changes (neuritic plaques and neurofibrillary tangles), Lewy body pathology and cerebrovascular disease and compared them to a control group of older licenced drivers (23M:5F) who died of other causes. The prevalence of moderate or severe neuritic plaque pathology was less than expected for the general population of this age and there was no difference between the groups. However, mild neuritic plaque pathology was increased for MVA deaths compared to controls. There was no evidence of vascular dementia or dementia with Lewy bodies. The current mandatory age-related re-licencing procedures in NSW may contribute to the low percentage of drivers with severe pathology. Further research into the role of mild pathology in cognitive impairment and older drivers is warranted.

Cardiovascular and temperature changes in spinal cord injured rats at rest and during autonomic dysreflexia.

In patients with high spinal cord injuries autonomic dysfunction can be dangerous, leading to medical complications such as postural hypotension, autonomic dysreflexia and temperature disturbance. While animal models have been developed to study autonomic dysreflexia, associated temperature changes have not been documented. Our aim here was to use radiotelemetry and infrared thermography in rodents to record the development of cardiovascular and skin temperature changes following complete T4 transection. In adult male Wistar rats (n=5), responses were assessed prior to spinal cord injury (intact) and for 6 weeks following injury. Statistical analysis by a repeated-measure ANOVA revealed that following spinal cord injury (SCI), rats exhibited decreased mean arterial pressure (MAP, average decrease of 26 mmHg; P<0.035) and elevated heart rate (HR, average increase of 65 bpm, P<0.035) at rest. The basal core body temperature following SCI was also significantly lower than intact levels (-0.9 degrees C; P<0.0035). Associated with this decreased basal core temperature following SCI was an increased skin temperature of the mid-tail and hindpaw (+5.6 and +4.0 degrees C, respectively; P<0.0003) consistent with decreased cutaneous vasoconstrictor tone. Autonomic dysreflexia, in response to a 1 min colorectal distension (25 mmHg), was fully developed by 4 weeks after spinal cord transection, producing increases in MAP greater than 25 mmHg (P<0.0003). In contrast to the tachycardia seen in intact animals in response to colorectal distension, SCI animals exhibited bradycardia (P<0.0023). During episodes of autonomic dysreflexia mid-tail surface temperature decreased (approximately -1.7 degrees C, P<0.012), consistent with cutaneous vasoconstriction. This is the first study to compare cardiovascular dysfunction with temperature changes following spinal cord transection in rats.

Increased neurofibrillary tangles in the brains of older pedestrians killed in traffic accidents.

BACKGROUND/AIMS: Older people are over-represented in pedestrian fatalities, and it has been suggested that the presence of cognitive impairment or dementia in these individuals may contribute to their accidents. Using neuropathological methods, we aimed to compare the prevalence of dementia pathology in fatally injured older pedestrians with similarly aged ambulatory subjects who died from other causes. METHODS: The brains of 52 pedestrians (65-93 years) and 52 controls (65-92 years) were assessed for neurofibrillary tangles (NFT), neuritic plaques, Lewy bodies and vascular lesions using established neuropathological criteria. RESULTS: The examination for Alzheimer's disease (AD) pathology showed that 43% of the pedestrians had NFT scores of III-VI using Braak and Braak staging, compared with 23% of the controls (p < 0.05, Fisher's exact test), indicating incipient, possible or probable AD. There were no differences in the prevalence of pathology for vascular dementia or dementia with Lewy bodies. CONCLUSION: These results suggest that cognitive decline associated with AD, even in the earliest stages of the disease, may be a factor in fatal traffic accidents for older pedestrians. Special measures for pedestrian safety are necessary in areas with high densities of older citizens and especially for those diagnosed as having a mild cognitive impairment or AD.

Developmental onset of functional activity in the wallaby whisker cortex in response to stimulation of the infraorbital nerve.

This study used the extrauterine development of a marsupial wallaby to investigate the onset of functional activity in the somatosensory pathway from the whiskers. In vivo recordings were made from the somatosensory cortex from postnatal day (P) 55 to P138, in response to electrical stimulation of the infraorbital nerve supplying the mystacial whiskers. Current source density analysis was used to localize the responses within the cortical depth. This was correlated with development of cortical lamination and the onset of whisker-related patches, as revealed by cytochrome oxidase. The earliest evoked activity occurred at P61, when layers 5 and 6 are present, but layer 4 has not yet developed. This activity showed no polarity reversal with depth, suggesting activity in thalamocortical afferents. By P72 synaptic responses were detected in developing layer 4 and cytochrome oxidase showed the first hint of segregation into whisker-related patches. These patches were clear by P86. The evoked response at this age showed synaptic activity first in layer 4 and then in deep layer 5/upper layer 6. With maturity, responses became longer lasting with a complex sequence of synaptic activity at different cortical depths. The onset of functional activity is coincident with development of layer 4 and the onset of whisker-related pattern formation. A similar coincidence is seen in the rat, despite the markedly different chronological timetable, suggesting similar developmental mechanisms may operate in both species.

Cholinergic depletion by IgG192-saporin retards development of rat barrel cortex.

This study examines the role of cholinergic projections from the basal forebrain on development of the rodent barrel cortex. Pups were administered the immunotoxin IgG192-saporin (0.1 microg) intraventricularly at postnatal day (P) 0 and sacrificed at P1-P7. One ventricle was injected with saporin while the other side received saline, allowing comparison between the two sides of the same animal, as well as with controls receiving saline only. Compared to control animals, neuronal loss in the basal forebrain was present on both sides of saporin-treated pups but was significantly greater on the toxin-treated side, in all age groups and regions sampled. Depletion of acetylcholine did not prevent the formation of the barrel pattern, however it delayed its emergence by approximately 1 day. At P4, the thickness of layer IV barrel cortex was also significantly reduced; this reduction was undetectable by P7. From P3 to P5, the ratios of intensity of staining for acetylcholinesterase between the barrel centres and septa on the toxin-treated side were significantly lower than those on the saline side, although normal densities were present by P7. Thus, the depletion of cholinergic innervation at birth causes a transient delay in the development of the barrel pattern during the first postnatal week.