Predictive model for the preparedness level of the family caregiver.

BACKGROUND: Many caregivers are insufficiently prepared, and little is known about measures that can be employed to enhance their preparedness. AIM: The aim of this study was to explore the factors associated with caregiver preparedness and establish a predictive model including the relationship between preparedness, burden, resilience and anxiety. DESIGN: A cross-sectional design was used. METHODS: The sample included 172 family caregivers who were selected from one private hospital and daytime nursing centres. Caregivers were recruited from 2018 to 2019; they completed assessments for caregiver preparedness, anxiety, resilience and burden. A multiple linear regression analysis was performed to identify the factors associated with preparedness. RESULTS: Preparedness was significantly associated with high levels of resilience and a low level of burden, while it was not associated with anxiety. Caregivers' gender, experience and cohabitation status were the main predictors. Resilience is an explanatory factor for caregiver preparedness in the predictive model. CONCLUSION: The demographic variables related to preparedness can be used to guide efforts to meet the needs of vulnerable caregivers. A caregiver's preparedness depends on their level of burden and resilience. Nursing interventions focused on these aspects could make the caregiver's role easier and improve the quality of care provided.

Development and psychometric testing of the Spanish version of the Caregiver Preparedness Scale.

AIM: To psychometrically test the Spanish version of the Caregiver Preparedness Scale (CPS) and document the preparedness level of caregivers. DESIGN: A descriptive and validation study. METHOD: Purposive sampling method was used to select 171 family caregivers Spain. The scale was cross-culturally adapted through a process that included translation, comparison with versions in other languages and back-translation, review, pre-testing and validity, and reliability tests. RESULTS: The Spanish family caregivers are mainly female (79%) and married (75%). The Spanish version of the CPS presents changes with respect to the original. Confirmatory factor analysis supported the single-factor model. Analysis of internal consistency yielded a Cronbach's α of 0.89. Significant correlations (p < .01) with other scales supported convergent validity. A descriptive analysis of the validated scale showed average levels of preparation (2.16 out of 4). Caregivers felt better prepared to attend to the patient's physical needs than emotional or spiritual needs.

Stress Increases the Negative Effects of Chronic Pain on Hippocampal Neurogenesis.

BACKGROUND: Patients with chronic pain often suffer from affective disorders and cognitive decline, which significantly impairs their quality of life. In addition, many of these patients also experience stress unrelated to their illness, which can aggravate their symptoms. These nociceptive inputs are received by the hippocampus, in which maladaptive neuroplastic changes may occur in the conditions of chronic pain. The hippocampus is a structure involved in emotionality, learning, and memory, and the proliferating cells in the granular layer of the hippocampal dentate gyrus respond to chronic pain by slowing their turnover. However, whether the maturation, survival, and integration of newborn cells in the hippocampus are affected by chronic pain remains unclear. In addition, it is unknown whether an added stress may increase this effect. METHODS: We have evaluated the proliferation, differentiation, and survival of newborn hippocampal cells in a rat model of neuropathic pain (chronic constriction injury), with or without stress (chronic immobilization), by assessing the incorporation of bromodeoxyuridine into proliferating cells and immunostaining. RESULTS: The data obtained indicated that there was a decrease in the number of proliferating cells 8 days after nerve injury in animals subjected to neuropathic pain, an effect that was exacerbated by stress. Moreover, 4 weeks after nerve injury, neuropathic pain was associated with a loss of neuroblasts and the reduced survival of new mature neurons in the hippocampal granular layer, phenomena that also were increased by stress. By contrast, the rate of differentiation was not affected in this paradigm. CONCLUSIONS: Neuropathic pain negatively influences hippocampal neurogenesis (proliferation and survival), and this effect is exacerbated by stress. These neuroplastic changes may account for the affective and cognitive impairment seen in patients with chronic pain.

ADAM-17/tumor necrosis factor-α-converting enzyme inhibits neurogenesis and promotes gliogenesis from neural stem cells.

Neural precursor cells (NPCs) are activated in central nervous system injury. However, despite being multipotential, their progeny differentiates into astrocytes rather than neurons in situ. We have investigated the role of epidermal growth factor receptor (EGFR) in the generation of non-neurogenic conditions. Cultured mouse subventricular zone NPCs exposed to differentiating conditions for 4 days generated approximately 50% astrocytes and 30% neuroblasts. Inhibition of EGFR with 4-(3-chloroanilino)-6,7-dimethoxyquinazoline significantly increased the number of neuroblasts and decreased that of astrocytes. The same effects were observed upon treatment with the metalloprotease inhibitor galardin, N-[(2R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl]-L-tryptophan methylamide (GM 6001), which prevented endogenous transforming growth factor-α (TGF-α) release. These results suggested that metalloprotease-dependent EGFR-ligand shedding maintained EGFR activation and favored gliogenesis over neurogenesis. Using a disintegrin and metalloprotease 17 (ADAM-17) small interference RNAs transfection of NPCs, ADAM-17 was identified as the metalloprotease involved in cell differentiation in these cultures. In vivo experiments revealed a significant upregulation of ADAM-17 mRNA and de novo expression of ADAM-17 protein in areas of cortical injury in adult mice. Local NPCs, identified by nestin staining, expressed high levels of ADAM-17, as well as TGF-α and EGFR, the three molecules necessary to prevent neurogenesis and promote glial differentiation in vitro. Chronic local infusions of GM6001 resulted in a notable increase in the number of neuroblasts around the lesion. These results indicate that, in vivo, the activation of a metalloprotease, most probably ADAM-17, initiates EGFR-ligand shedding and EGFR activation in an autocrine manner, preventing the generation of new neurons from NPCs. Inhibition of ADAM-17, the limiting step in this sequence, may contribute to the generation of neurogenic niches in areas of brain damage.

Age-dependent effect of nitric oxide on subventricular zone and olfactory bulb neural precursor proliferation.

Nitric oxide (NO) synthase (NOS) is developmentally regulated in the embryonic brain, where NO participates in cell proliferation, survival, and differentiation. In adults, NO inhibits neurogenesis under physiological conditions. This work investigates whether the NO action is preserved all along development up to adulthood or whether its effects in adults are a new feature acquired during brain maturation. The relationship between nitrergic neurons and precursors, as well as the functional consequences of pharmacological NOS inhibition, were comparatively analyzed in the subventricular zone (SVZ) and olfactory bulb (OB) of postnatal (P7) and adult (>P60) mouse brains. The SVZ was markedly reduced between P7 and adults, and, at both ages, neurons expressing neuronal NOS (nNOS) were found in its striatal limits. In postnatal mice, these nitrergic neurons contained PSA-NCAM, and their projections were scarce, whereas, in adults, mature nitrergic neurons, devoid of PSA-NCAM, presented abundant neuropil. In the OB, local proliferation almost disappeared in the transition to adulthood, and periglomerular nitrergic neurons, some of which were PSA-NCAM positive, were found in postnatal and adult mice. Administration of the NOS inhibitor L-NAME did not affect cell proliferation in the SVZ or in the OB of postnatal mice, whereas it significantly enhanced the number of mitotic cells in both regions in adults. Thus, the NO action on SVZ neurogenesis is a phenomenon that appears after the postnatal age, which is probably due to the germinal layer size reduction, allowing exposure of the NO-sensitive neural precursors to the NO produced in the SVZ-striatum limits.

Nitric oxide decreases subventricular zone stem cell proliferation by inhibition of epidermal growth factor receptor and phosphoinositide-3-kinase/Akt pathway.

Nitric oxide (NO) inhibits proliferation of subventricular zone (SVZ) neural precursor cells in adult mice in vivo under physiological conditions. The mechanisms underlying this NO effect have now been investigated using SVZ-derived neural stem cells, which generate neurospheres in vitro when stimulated by epidermal growth factor (EGF). In these cultures, NO donors decreased the number of newly formed neurospheres as well as their size, which indicates that NO was acting on the neurosphere-forming neural stem cells and the daughter neural progenitors. The effect of NO was cytostatic, not proapoptotic, and did not involve cGMP synthesis. Neurosphere cells expressed the neuronal and endothelial isoforms of NO synthase (NOS) and produced NO in culture. Inhibition of NOS activity by N(omega)-nitro-L-arginine methylester (L-NAME) promoted neurosphere formation and growth, thus revealing an autocrine/paracrine action of NO on the neural precursor cells. Both exogenous and endogenous NO impaired the EGF-induced activation of the EGF receptor (EGFR) tyrosine kinase and prevented the EGF-induced Akt phosphorylation in neurosphere cells. Inhibition of the phosphoinositide-3-kinase (PI3-K)/Akt pathway by LY294002 significantly reduced the number of newly formed neurospheres, which indicates that this is an essential pathway for neural stem cell self-renewal. Chronic administration of l-NAME to adult mice enhanced phospho-Akt staining in the SVZ and reduced nuclear p27(Kip1) in the SVZ and olfactory bulb. The inhibition of EGFR and PI3-K pathway by NO explains, at least in part, its antimitotic effect on neurosphere cells and may be a mechanism involved in the physiological role of NO as a negative regulator of SVZ neurogenesis in adult mice.

Chronic inhibition of nitric oxide synthesis enhances both subventricular zone neurogenesis and olfactory learning in adult mice.

The ability to generate new neurons during the course of adult life is preserved in the subventricular zone of the lateral ventricles and the dentate gyrus of the hippocampus in the mammalian brain. These two regions constitute specifically regulated neurogenic niches, and provide newborn neurons involved in olfactory and spatial learning, respectively. Nitric oxide (NO) is a negative regulator of neurogenesis in the subventricular zone, whereas its role in the dentate gyrus remains controversial. Using systemic administration of NO synthase (NOS) inhibitors to chronically inhibit NO production, we increased neural precursor proliferation in the subventricular zone as well as neurogenesis in the olfactory bulb, without modifying the number of mitotic cells or the granular cell layer thickness in the dentate gyrus. The same treatment specifically improved olfactory learning performance, whereas spatial learning and memory was unchanged, thus demonstrating that olfactory memory is closely associated with the level of ongoing neurogenesis in the subventricular zone-olfactory bulb. The anatomical specificity of the NOS inhibitor actions was not due to differences in the availability of NO, as demonstrated by immunohistochemical detection of neuronal NOS and S-nitrosylated proteins in both regions. Remarkably, the distinct NO sensitivity might result from a differential expression of epidermal growth factor receptor in precursor cells in both regions, as the proliferative effect of NOS inhibitors in the subventricular zone was restricted to the cells that expressed this receptor.

Nitric oxide is a physiological inhibitor of neurogenesis in the adult mouse subventricular zone and olfactory bulb.

The subventricular zone of the rodent brain retains the capacity of generating new neurons in adulthood. The newly formed neuroblasts migrate rostrally toward the olfactory bulb, where they differentiate as granular and periglomerular interneurons. The reported presence of differentiated neurons expressing the neuronal isoform of nitric oxide synthase (NOS) in the periphery of the neurogenic region and the organization of their varicose axons as a network in which the precursors are immersed raised the hypothesis that endogenous nitric oxide (NO) may participate in the control of neurogenesis in the subventricular zone. Systemic administration of the NOS inhibitors N(omega)-nitro-L-arginine methyl ester or 7-nitroindazole to adult mice produced a dose- and time-dependent increase in the number of mitotic cells in the subventricular zone, rostral migratory stream, and olfactory bulb, but not in the dentate gyrus of the hippocampus, without affecting apoptosis. In the subventricular zone, this effect was exerted selectively on a precursor subpopulation expressing nestin but not neuronal or glial cell-specific proteins. In addition, in the olfactory bulb, analysis of maturation markers in the newly generated neurons indicated that chronic NOS inhibition caused a delay in neuronal differentiation. Postmitotic cell survival and migration were not affected when NO production was impaired. Our results suggest that NO, produced by nitrergic neurons in the adult mouse subventricular zone and olfactory bulb, exerts a negative control on the size of the undifferentiated precursor pool and promotes neuronal differentiation.