Differential Regional Responses in Soluble Monomeric Alpha Synuclein Abundance Following Traumatic Brain Injury.

Alpha synuclein (α-synuclein) is a neuronal protein found predominately in presynaptic terminals. While the pathological effect of α-synuclein aggregates has been a topic of intense study in several neurodegenerative conditions, less attention has been placed on changes in monomeric α-synuclein and related physiological consequences on neuronal function. A growing body of evidence supports an important physiological role of α-synuclein in neurotransmission. In the context of traumatic brain injury (TBI), we hypothesized that the regional abundance of soluble monomeric α-synuclein is altered over a chronic time period post-injury. To this end, we evaluated α-synuclein in the cortex, hippocampus, and striatum of adult rats at 6 h, 1 day, 1, 2, 4, and 8 weeks after controlled cortical impact (CCI) injury. Western blot analysis demonstrated decreased levels of monomer α-synuclein protein in the ipsilateral hippocampus at 6 h, 1 day, 1, 2, and 8 weeks, as well as in the ipsilateral cortex at 1 and 2 weeks and in the ipsilateral striatum at 6 h after CCI compared with sham animals. Immunohistochemical analysis revealed lower α-synuclein and a modest reduction in synaptophysin staining in the ipsilateral hippocampus at 1 week after CCI compared with sham animals, with no evidence of intracellular or extracellular α-synuclein aggregates. Collectively, these findings demonstrate that monomeric α-synuclein protein abundance in the hippocampus is reduced over an extensive (acute-to-chronic) post-injury interval. This deficit may contribute to the chronically impaired neurotransmission known to occur after TBI.

Not all cementless femoral stems are created equal but the results may be comparable.

AIMS: The aim of this study was to compare the survivorship and radiographic outcomes at ten-year follow-up of three prospective consecutive series of patients each of which received a different design of cementless femoral components for total hip arthroplasty (THA). PATIENTS AND METHODS: In Cohort 1, 91 consecutive patients (100 hips) underwent THA with a cementless porous-coated anatomic femoral stem (PCA) between October 1983 and January 1986. In Cohort 2, 86 consecutive patients (100 hips) underwent THA with an extensively porous-coated cementless femoral stem (Prodigy) between June 1994 and October 1997. In Cohort 3, 88 consecutive patients (100 hips) underwent THA with a proximally porous-coated triple-tapered cementless stem (Summit) between April 2002 and October 2003. All three groups underwent prospective clinical and radiographic evaluation. RESULTS: Kaplan-Meier survivorship analysis of Cohort 1 was 91% (95% confidence interval (CI) 88 to 94) with an endpoint of revision for any reason and 97% (95% CI 95 to 99) with aseptic loosening as the endpoint. Survivorship of Cohort 2 was 88% (95% CI 79 to 97) for revision for any reason and 100% for aseptic loosening. Survivorship of Cohort 3 was 95% (95% CI 91 to 99) for revision for any reason and 100% with aseptic loosening as the endpoint. CONCLUSION: With revision for aseptic loosening of the femoral component as the endpoint, the three femoral components with different design philosophies demonstrated excellent survivorship, ranging from 97% to 100% at ten years. Cite this article: Bone Joint J 2017;99-B(1 Supple A):14-17.

Developmental assessment of hypothalamic tuberoinfundibular dopamine in prolactin-deficient dwarf mice.

Development of the hypophysiotropic hypothalamus in PRL-deficient Ames dwarf (df/df) mice was examined for steady state dopamine (DA) by visualization using formaldehyde-induced catecholamine histofluorescence and by quantification using catecholamine HPLC at selected postnatal ages (7, 14, 21, 30, and 90 days). Phenotypically normal (DF/?) littermate mice were compared with dwarfs by both methods at each age. The studies were designed to investigate whether the known deficiency in hypothalamic tuberoinfundibular DA in adult dwarfs is present neonatally or develops over the postnatal period. The anterior pituitary of each mouse was processed for GH and PRL immunocytochemistry. At 7 days of age, GH immunostaining was robust, and scattered PRL-positive cells were noted in DF/? pituitary. Homogeneously distributed PRL cells increased in number through 30 days of age in normal mice. Neither GH nor PRL immunoreactivity was present in df/df mice at any age. At 7, 14, and 21 days of age, hypothalamic DA tuberoinfundibular histofluorescence was comparable in df/df and DF/? mice. At 90 days of age, tuberoinfundibular histofluorescence in normal mice remained intense, but was virtually undetectable in dwarfs. The developmental change affected only tuberoinfundibular neurons, since DA histofluorescence in nonhypophysiotropic areas, such as substantia nigra (SN), was qualitatively comparable for df/df and DF/? for all ages examined. Norepinephrine (NE) fluorescence in hypothalamus was also comparable for df/df and DF/?. Catecholamine HPLC provided quantitative confirmation of histofluorescence observations. DA and NE levels in both hypothalamus and ventral midbrain, including SN, increased during development in both df/df and DF/? brains. NE levels were not different between dwarf and normal animals at any age in either medial basal hypothalamus (MBH) or SN. The DA concentration in SN was not different between df/df and DF/? at any age examined. MBH DA was comparable in df/df and DF/? mice at 7, 14, and 21 days of age; at 30 and 90 days, MBH DA was markedly lower (P < 0.001) in dwarf than in normal mice. Although MBH DA in dwarfs was comparable to that in normal mice at 21 days, the increase in dwarfs between 14 and 21 days was not statistically significant. Thus, the hypothalamic DA deficit that exists in adult dwarf mice is not present neonatally and represents a failure to increase DA compared with normal mice after 14 days of age. The failure of continued development of hypophysiotropic tuberoinfundibular DA neurons in dwarf mice is correlated chronologically with absent pituitary PRL production.

Effect of surgical deafferentation of the hypothalamic supraoptic nucleus on urinary vasopressin levels in twenty-month-old rats.

Indices of water balance (daily water consumption, urine volume, and urine osmolality), and vasopressin (VP) urinary excretion were measured in 3-month-old (m.o.) and 20 m.o. F344 rats after neurosurgical lesion of noradrenergic afferents to the supraoptic nucleus (SON) in the medial forebrain bundle (mfb), in order to assess whether morphological denervation (21) was functionally effective. Lesion of the mfb was accomplished using a mechanical knife cut placed stereotaxically medial and caudal to SON. The experiment was performed three times. Morphological evaluation consistently indicated a marked depletion of noradrenergic afferents in SON after lesion placement. The effect of the lesion on daily excreted VP was assessed by paired t-test, using means of equal numbers of urinary VP measurements representing 13-15 days each pre- and postsurgically for each animal. The postsurgical interval for assessing the functional effect of the lesion was chosen based upon morphological evidence for mfb regeneration at 14 days (21). Three m.o. rats showed comparable urinary VP levels before (mean = 328.4 +/- 97.3 pg/24 hr/100 g b.wt., for 10 rats for 2 weeks) and after (354.7 +/- 63.0 pg/24 hr/100 g b.wt.) lesion placement. In 20 m.o. rats, overall mean postsurgical VP excretion was 199.4 +/- 44.8 pg for 15 rats for 2 weeks, compared with a presurgical mean of 343.2 +/- 86.2 pg/24 hr/100 g b.wt. Mean urine VP was lower in 20 m.o. rats in each of three experiments; VP levels after lesion in 3 m.o. rats was lower in 2, but higher in one experiment; mean differences were not statistically significant for treatment (lesion) effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasopressin in aged rats: longitudinal studies of vasopressin excretion in Sprague-Dawley and Fischer 344 strains.

In order to provide physiological baseline values for future experimental procedures, indices of vasopressin secretion were assessed in male Sprague-Dawley (SD) and Fischer 344 (F344) rats at 3 and 20 months of age. Daily water intake, urine volume, urine osmolality, and urinary vasopressin excretion were monitored in SD rats for 30 days, and in F344 rats for 60 days. In the SD strain, daily water and urine volumes, expressed as ml/24 hr/100 g b.wt., were consistently lower in aged animals, as was a calculation of water balance (water intake-urine output volumes/24 hr). Although mean VP concentration in urine appeared higher in aged rats (33.9 +/- 20.4 pg/ml) than in young (16.3 +/- 7.7 pg/ml), total daily VP excretion was comparable for both ages when expressed as a function of body weight [80.6 +/- 37.3 pg for 3 months old (m.o.) and 81.9 +/- 47.2 pg/24 hr/100 g b.wt. for 3 and 20 m.o. respectively]. Young and old F344 males showed comparable daily drinking and urine volumes, and water balance, during two months of monitoring, but VP excretion was lower (p less than 0.025) in aged rats (83.8 +/- 19.0 pg/24 hr/100 g b.wt.) than in 3 m.o. rats (213.0 +/- 48.1 pg/24 hr/100 g b.wt.). Urine VP concentration was comparable (69.6 +/- 20.6 for 3 m.o.; 59.8 +/- 25.6 pg/ml for 20 m.o.). Mean urine osmolality was not significantly different among groups. Urine osmolality and daily urine volumes showed a significant correlation with daily VP excretion among young, but not aged, rats of both strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothalamic dopaminergic neurons in prolactin-deficient Ames dwarf mice: localization and quantification of deficit by tyrosine hydroxylase immunocytochemistry.

Hypothalamic tuberoinfundibular prolactin-inhibiting neurons show decreased levels and synthesis of dopamine in two types of genetically prolactin-deficient dwarf mice (Snell, Ames) which arise from separate mutations. A reduction to 2% of normal in this neuronal population has been quantified for Snell dwarfs. The present study was undertaken in order to quantify morphometrically the deficit and its distribution in Ames dwarf mice, including comparisons of sex and adult age. The brains of dwarf (df/df) and normal phenotypic (DF/?) sibling mice of both sexes from 4 to 16 months of age were immunostained for tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis; neuronal perikarya were counted in coronal sections of tuberoinfundibular arcuate nucleus (area A12), medial zona incerta (A13) and anterior periventricular (A14) hypothalamic areas at 180 microns rostral-to-caudal intervals. Normal (DF/?) mice exhibited no differences in neuron numbers, with regard to age or sex, in any of the three dopaminergic areas. In dwarf mice, a tendency toward decreased neuron numbers with age was statistically significant for area A14 only, and the size of the neuronal population in A12 was reduced in males compared with females. Total A12 neuron number in dwarfs was 48% of that in normal mice (P < 0.001). Periventricular (A14) perikaryal numbers were reduced slightly (P < 0.05) in dwarfs compared with normals. Numbers of A13 neurons were comparable for DF/? and df/df.(ABSTRACT TRUNCATED AT 250 WORDS)

Catecholamine reinnervation of supraoptic nucleus after deafferenting mechanical lesions and superior cervical ganglionectomy: histofluorescence and functional assessments in young adult and aged rats.

Catecholaminergic innervation of the hypothalamic vasopressin (VP)-secreting supraoptic nucleus (SON) was examined at selected intervals after deafferenting neurosurgical lesions, with respect to potential contribution of peripheral vascular sympathetic fibers. Young adult (3 months) and aged (20 months) male F344 rats were subjected to mechanical knife-cut lesion just caudal and medial to the SON, superior cervical ganglionectomy (SCGx), or both surgeries. SON and lesion sites were assessed at 4, 14, 30 or 45 days after surgery, by CA histofluorescence. Functional evaluation in rats subjected to chronic lesions consisted of monitoring water balance (water consumption and urine volumes, and urine osmolality and VP content) in individual rats for presurgical and postsurgical intervals. Histofluorescence evaluation showed that SCGx did not affect the overall SON fluorescence pattern, although a minor sympathetic contribution to that pattern was discerned by comparing SON in rats subjected to lesion alone vs SCGx + lesion. Morphological reinnervation of SON was accomplished at 30 days in young rats, and 45 days in aged rats, after both lesion and SCGx. In young rats, histofluorescence density 30 days after deafferentation was denser than the innervation pattern seen in intact (sham-lesioned) animals, while reinnervation at 45 days postsurgically in aged rats only approximated the presurgical pattern. Vasopressin excretion and corresponding water conservation measures were compromised by SON deafferentation at both ages; excreted VP levels and water balance did not rebound to presurgical values at chronic postsurgical intervals in either young or aged rats.(ABSTRACT TRUNCATED AT 250 WORDS)