Spatiotemporal dynamics of PDGFRß expression in pericytes and glial scar formation in penetrating brain injuries in adults.

AIMS: Understanding the spatiotemporal dynamics of reactive cell types following brain injury is important for future therapeutic interventions. We have previously used penetrating cortical injuries following intracranial recordings as a brain repair model to study scar-forming nestin-expressing cells. We now explore the relationship between nestin-expressing cells, PDGFRß+ pericytes and Olig2+ glia, including their proliferation and functional maturation. METHODS: In 32 cases, ranging from 3 to 461 days post injury (dpi), immunohistochemistry for PDGFRß, nestin, GFAP, Olig2, MCM2, Aquaporin 4 (Aq4), Glutamine Synthetase (GS) and Connexin 43 (Cx43) was quantified for cell densities, labelling index (LI) and cellular co-expression at the injury site compared to control regions. RESULTS: PDGFRß labelling highlighted both pericytes and multipolar parenchymal cells. PDGFRß LI and PDGFRß+ /MCM2+ cells significantly increased in injury Zones at 10-13 dpi with migration of pericytes away from vessels with increased co-localization of PDGRFß with nestin compared to control regions (P < 0.005). Olig2+ /MCM2+ cell populations peaked at 13 dpi with significantly higher cell densities at injury sites than in control regions (P < 0.01) and decreasing with dpi (P < 0.05). Cx43 LI was reduced in acute injuries but increased with dpi (P < 0.05) showing significant cellular co-localization with nestin and GFAP (P < 0.005 and P < 0.0001) but not PDGFRß. CONCLUSIONS: These findings indicate that PDGFRß+ and Olig2+ cells contribute to the proliferative fraction following penetrating brain injuries, with evidence of pericyte migration. Dynamic changes in Cx43 in glial cell types with dpi suggest functional alterations during temporal stages of brain repair.

A comparative study of the dentate gyrus in hippocampal sclerosis in epilepsy and dementia.

AIMS: Hippocampal sclerosis (HS) is long-recognized in association with epilepsy (HSE ) and more recently in the context of cognitive decline or dementia in the elderly (HSD ), in some cases as a component of neurodegenerative diseases, including Alzheimer's disease (AD) and fronto-temporal lobe dementia (FTLD). There is an increased risk of seizures in AD and spontaneous epileptiform discharges in the dentate gyrus of transgenic AD models; epilepsy can be associated with an age-accelerated increase in AD-type pathology and cognitive decline. The convergence between these disease processes could be related to hippocampal pathology. HSE typically shows re-organization of both excitatory and inhibitory neuronal networks in the dentate gyrus, and is considered to be relevant to hippocampal excitability. We sought to compare the pathology of HSE and HSD , focusing on re-organization in the dentate gyrus. METHODS: In nine post mortem cases with HSE and bilateral damage, 18 HSD and 11 controls we carried out immunostaining for mossy fibres (dynorphin), and interneuronal networks (NPY, calbindin and calretinin) on sections from the mid-hippocampal body. Fibre sprouting (FS) or loss of expression in the dentate gyrus was semi-quantitatively graded from grade 0 (normal) to grade 3 (marked alteration). RESULTS: Significantly more re-organization was seen with all four markers in the HSE than HSD group (P < 0.01). Mild alterations were noted in HSD group with dynorphin (FS in 3 cases), calretinin (FS in 6 cases), NPY (FS in 11 cases) and calbindin (loss in 10 cases). In eight HSD cases, alteration was seen with more than one antibody but in no cases were the highest grades seen. We also noted NPY and, to a lesser extent, calretinin labelling of Hirano bodies in CA1 of AD cases and some older controls, but not in HSE . CONCLUSION: Reorganization of excitatory and inhibitory networks in the dentate gyrus is more typical of HSE . Subtle alterations in HSD may be a result of increased hippocampal excitability, including unrecognized seizure activity. An unexpected finding was the identification of NPY-positive Hirano bodies in HSD but not HSE , which may be a consequence of the relative vulnerabilities of interneurons in these conditions.

Attitudes in the management of patients with dementia: comparison in doctors with and without special training.

OBJECTIVE: To explore by postal survey the different attitudes towards management of patients with dementia in physicians with and without dementia training. METHODS: A questionnaire was sent to 7669 members of the Hong Kong Medical Association, which represents 61% of all locally registered medical practitioners. RESULTS: In all, 448 questionnaires were returned (response rate: 6%). Among these, there were 34 questionnaires with missing data or the respondents indicated that they were either retired or not in practice. Therefore, only 414 questionnaires were used in analysis. Among these, 82 (20%) had received dementia training, 310 (75%) had not, and 22 (5%) did not indicate their choice. Twelve statements were used to explore various attitudes about dementia care. Exploratory factor analysis showed that there were 2 strong factors: confidence and negative views. The mean scores of these 2 factors were significantly different in physicians with and without dementia training. With respect to management of patients with dementia, dementia-trained physicians had significantly greater confidence (mean [standard deviation (SD)] = 5.21 [1.34]) than those who were non-trained (mean [SD] = 3.57 [1.40]; p < 0.001). Conversely, non-trained physicians had significantly stronger negative views (mean [SD] = 3.89 [1.24]) on dementia care than those who were trained (mean [SD] = 3.12 [1.36]; p < 0.001). DISCUSSION: These findings suggest that providing a certain level of dementia care training for physicians is an effective way to improve confidence in managing patients with dementia, and thereby decrease possible negative attitudes towards such care.

The psychometric properties of Chinese pain intensity verbal rating scale.

BACKGROUND: This study investigates the validity and reliability of the Chinese pain intensity verbal rating scale (C-PIVRS). METHODS: This is a correlational comparative study. Fifty Chinese adults were recruited by convenience. A pain source generator (precision pain source, PPS-3) was used to produce four levels of mechanical pain stimuli (350, 550, 750 and 950 g). The pain stimuli were applied to subjects' interphalangeal joints in random sequences to stimulate sensation of pain. The subjects then rated their pain intensity using both the C-PIVRS and the visual analog scale (VAS) for each stimulus. The pain scores obtained from the C-PIVRS were compared with the VAS for satisfactory level of reliability and validity. Test and re-test were applied to verify consistency between the two pain scales. RESULTS: The test/re-test correlation coefficients between the two pain scales were r = 0.92 (P < 0.001) and r = 0.91 (P < 0.001), respectively. This showed a good positive correlation. The intra-class correlation (ICC) ranged from 0.78 to 0.90, which indicated good reliability. In the factor analysis, a single factor emerged in each analysis. The first eigen values of each matrix were 3.42, 3.24, 3.17 and 3.29 for each level of pain stimulation. This indicated that both pain scales were assessing the same pain dimension. CONCLUSIONS: The two pain scales have a comparable level of reliability and validity for assessing pain intensity in Chinese adults.