IntroductionThe transactivation response element DNA-binding protein 43 kDa (TDP-43) is a major component of the ubiquitin-positive and tau-negative inclusions in frontotemporal lobar degeneration and sporadic amyotrophic lateral sclerosis (ALS). TDP-43 may accumulate in cases of Alzheimer’s disease (AD), Lewy body disease (LBD), and argyrophilic grain disease (AGD). However, few studies have focused on the incidence and extent of TDP-43 deposition in aging.ResultsWe analyzed 286 consecutive autopsy brains neuropathologically. Of these, 136 brains with pathologically minimal senile changes were designated as control elderly brains (78.5 ± 9.7 y). For comparison, we selected 29 AD, 11 LBD, and 11 AGD patients from this series of autopsy brains. Sections of the hippocampus, amygdala, medulla oblongata, and lumbar spinal cord were immunostained with anti-phosphorylated TDP-43 antibody (PSer409/410). TDP-43 immunoreactive structures were classified into four types: dystrophic neurites (DNs), neuronal or glial cytoplasmic inclusions, and intranuclear inclusions. TDP-43 immunoreactive structures were observed in 55/136 control elderly (40.0 %), 21/29 AD (72.4 %), 8/11 LBD (72.7 %), and 6/11 AGD (54.5 %) brains. TDP-43 immunoreactive structures in control elderly brains were mostly DNs. These DNs were predominantly present in the uncus of the anterior hippocampus over age 65. The frequency of cases with DNs in the amygdala of control elderly brains was less than that of AD, LBD, and AGD brains. The mean age at death was significantly higher in cases with TDP-43 immunoreactive structures than cases without them.ConclusionsIn conclusion, TDP-43 immunoreactive DNs may develop as a consequence of aging processes in the human brain. In particular, the uncus of the anterior hippocampus is an area highly susceptible to TDP-43 accumulation over age 65.

BackgroundLewy body–related α-synucleinopathy (LBAS, the abnormal accumulation of pathologic α-synuclein) is found in the central and peripheral nervous systems, including the spinal cord, dorsal root ganglia, and sympathetic ganglia, of Parkinson’s disease patients. However, few studies have focused on the distribution of LBAS in the spinal cord, primary sensory neurons, and preganglionic sympathetic nerves.ResultsWe analyzed 265 consecutive subjects with LBAS who underwent autopsy at a general geriatric hospital. LBAS in the spinal cord was significantly associated with that in the lower brainstem regions that are directly connected to the spinal cord (i.e., the medullary reticular formation and locus ceruleus), but it was not associated with the olfactory bulb–amygdala system, which is not directly connected to the spinal cord, suggesting that the lower brainstem is a key structure regarding the spread of LBAS to the spinal cord. In the primary sensory neurons, most subjects with LBAS in the dorsal root ganglia had LBAS in the dorsal root, and all subjects with LBAS in the dorsal root also had LBAS in the dorsal horn, suggesting that LBAS spreads retrogradely from the axonal terminals of the dorsal horn to the somata of the dorsal root ganglia via the dorsal root. In the preganglionic sympathetic nerves, the LBAS in the sympathetic ganglia preceded that in the nucleus of the intermediolateral column of the thoracic cord, suggesting that LBAS spreads retrogradely through the preganglionic sympathetic nerves.ConclusionsLBAS in the spinal cord was associated with the lower regions of the brainstem, but not with the olfactory bulb or amygdala. LBAS may spread centrifugally along the primary sensory neurons, whereas it may spread centripetally along the preganglionic sympathetic nerves.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-015-0236-9) contains supplementary material, which is available to authorized users.

We detected Lewy body pathology in the olfactory epithelium in six of the eight patients with Parkinson's disease and in one patient with incidental Lewy body pathology.

A previous study reported that a massive cerebral infarct in the territory of the middle cerebral artery (MCA) may be associated with development of neurofibrillary tangles (NFTs) in the ipsilateral basal nucleus of Meynert (BNM). We analyzed 19 cases of an MCA territory infarct and 12 with a putaminal hemorrhage (mean age 82.5 years; female/male ratio 8/23; mean time from stroke onset to autopsy 4182 days). In both groups, 74–100% had a significantly higher rate of phosphorylated tau immunoreactive or Gallyas Braak silver stain-positive neurons on the BNM-affected side than on the BNM-unaffected side. These NFTs were immunoreactive for anti-RD3 and anti-RD4 antibodies, and a triple-band pattern was observed by immunoblot analysis with anti-tau antibody. Most NFTs might be formed within the 5–10 years after stroke onset. There were significantly more TAR DNA-binding protein 43 (TDP43) immunoreactive structures on the BNM-affected side than on the BNM-unaffected side. We showed that many NFTs with TDP43-immunoreactive structures were observed in the ipsilateral BNM associated with a massive cerebral infarct in the MCA territory or a putaminal hemorrhage.

No abstract

Intradermal injection of capsaicin induces a region of visual flare (neurogenic inflammation) and regions with modality specific hyperalgesia. Their temporal and spatial profiles have been studied to elucidate the mechanism behind neurogenic inflammation and hyperalgesia. Until today, the flare response has mainly been quantified by visual inspection. However, recent developments of thermography and laser-Doppler flowmetry have facilitated quantitative measurement of the neurogenic inflammation. The purpose of the present study was (1). to measure the temporal and spatial profiles of neurogenic inflammation and hyperalgesia induced by capsaicin by using thermography/laser-Doppler flowmetry and various sensory tests, and (2). to correlate the parameters related to neurogenic inflammation with the areas of secondary hyperalgesia. Eight healthy volunteers were injected intradermally with 250 microg of capsaicin. Five minutes after the injection, temperature and blood flow were measured by thermography and a laser-Doppler flowmetry, and followed by assessment of visual flare and hyperalgesia. Punctate hyperalgesia, stroking hyperalgesia, and heat hyperalgesia were assessed by von Frey hair, cotton swab, and radiant heat stimulator, respectively. This procedure was repeated 30 and 60 min after the injection. A significant increase in blood flow and temperature was detected by laser-Doppler flowmetry and thermography (F=102.08, P<0.001, and F=8.46, P=0.002, respectively). Throughout the experiment, the areas of visual flare, stroking hyperalgesia, and punctate hyperalgesia were covered by the area of significantly increased blood flow detected 5 min after the injection. The intensity of pain to heat stimuli significantly increased over time at the distal site and the proximal site (P<0.05). However, there was no significant difference between the pain intensity to radiant heat stimuli inside/outside the area of punctate hyperalgesia. These results seem to indicate that a possible contribution of neurogenic inflammation to secondary hyperalgesia (especially to radiant heat stimuli) must be reconsidered.

No abstract

The combination of glutamate injection into latent MTrPs together with the breath-hold manoeuvre did not result in further decrease in skin temperature and blood flow, indicating that sympathetic vasoconstrictor activity is fully activated by nociceptive stimulation of MTrPs.