Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological ...changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and (18)F-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.
Objective
The progression of Alzheimer’s disease (AD) is associated with impaired nutritional status. New methods, such as deep brain stimulation (DBS), are currently being tested to decrease the ...progression of AD. DBS is an approved method in the treatment of Parkinson’s disease, and its suitability for the treatment of AD patients is currently under experimental investigation. To evaluate the advantages and disadvantages of this new treatment, it is important to assess potential side effects of DBS regarding the nucleus basalis of Meynert; this new treatment is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in AD. This study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status.
Design
A 1-year phase I proof-of-concept study.
Setting
The Department of Psychiatry and Psychotherapy at the University of Cologne.
Participants
We assessed a consecutive sample of patients with mild to moderate AD (n=6) who fulfilled the inclusion criteria and provided written informed consent. Intervention: Bilateral low-frequency DBS of the nucleus basalis of Meynert.
Measurements
Nutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate.
Results
With a normal body mass index (BMI) at baseline (mean 23.75 kg/m
2
) and after 1 year (mean 24.59 kg/m
2
), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman’s rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman’s rho = −0.829, p = 0.042).
Conclusion
Patients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies.
In the past decade deep brain stimulation (DBS)-the application of electrical stimulation to specific target structures via implanted depth electrodes-has become the standard treatment for medically ...refractory Parkinson's disease and essential tremor. These diseases are characterized by pathological synchronized neuronal activity in particular brain areas. We present an external trial DBS device capable of administering effectively desynchronizing stimulation techniques developed with methods from nonlinear dynamics and statistical physics according to a model-based approach. These techniques exploit either stochastic phase resetting principles or complex delayed-feedback mechanisms. We explain how these methods are implemented into a safe and user-friendly device.
OBJECTIVEThe progression of Alzheimer's disease (AD) is associated with impaired nutritional status. New methods, such as deep brain stimulation (DBS), are currently being tested to decrease the ...progression of AD. DBS is an approved method in the treatment of Parkinson's disease, and its suitability for the treatment of AD patients is currently under experimental investigation. To evaluate the advantages and disadvantages of this new treatment, it is important to assess potential side effects of DBS regarding the nucleus basalis of Meynert; this new treatment is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in AD. This study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status.DESIGNA 1-year phase I proof-of-concept study.SETTINGThe Department of Psychiatry and Psychotherapy at the University of Cologne.PARTICIPANTSWe assessed a consecutive sample of patients with mild to moderate AD (n=6) who fulfilled the inclusion criteria and provided written informed consent.INTERVENTIONBilateral low-frequency DBS of the nucleus basalis of Meynert.MEASUREMENTSNutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate.RESULTSWith a normal body mass index (BMI) at baseline (mean 23.75 kg/m²) and after 1 year (mean 24.59 kg/m²), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman's rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman's rho = -0.829, p = 0.042).CONCLUSIONPatients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies.
An under-agarose chemotaxis assay was used to investigate whether unrestricted somatic stem cells (USSC) that were recently characterized in human cord blood are attracted by neuronal injury in ...vitro. USSC migrated toward extracts of post-ischemic brain tissue of mice in which stroke had been induced. Moreover, apoptotic neurons secrete factors that strongly attracted USSC, whereas necrotic and healthy neurons did not. Investigating the expression of growth factors and chemokines in lesioned brain tissue and neurons and of their respective receptors in USSC revealed expression of hepatocyte growth factor (HGF) in post-ischemic brain and in apoptotic but not in necrotic neurons and of the HGF receptor c-MET in USSC. Neuronal lesion-triggered migration was observed in vitro and in vivo only when c-MET was expressed at a high level in USSC. Neutralization of the bioactivity of HGF with an antibody inhibited migration of USSC toward neuronal injury. This, together with the finding that human recombinant HGF attracts USSC, document that HGF signaling is necessary for the tropism of USSC for neuronal injury. Our data demonstrate that USSC have the capacity to migrate toward apoptotic neurons and injured brain. Together with their neural differentiation potential, this suggests a neuroregenerative potential of USSC. Moreover, we provide evidence for a hitherto unrecognized pivotal role of the HGF/c-MET axis in guiding stem cells toward brain injury, which may partly account for the capability of HGF to improve function in the diseased central nervous system.
To apply digital signal acquisition and analyzing techniques to the collection and interpretation of electromyographic data of the cavernous body.
Electromyographic recordings were performed in the ...cavernous bodies of anesthetized, spontaneously breathing dogs under resting conditions and after intracavernous pharmacostimulation with norepinephrine, angiotensin II, phentolamine/papaverine, diethylether and T61.
Resting corpus cavernosum activity was ill-coordinated and provided little information. Signal energy was confined largely to the range below 20 Hz. Pharmacostimulation with norepinephrine or angiotensin increased frequency and amplitude of the potential transients and decreased the random components. Administration of a combination of phentolamine and papaverine made the signals very regular and increased periodicity. Blockade of electrical membrane events with diethylether removed all signal components except for electrical and biological noise.
Our findings indicate that electromyograms from the corpus cavernosum can be recorded even under adverse conditions. Signal properties, however, are such that the application of computer-aided data processing and analysis to the evaluation of these myograms is imperative.
The ionic mechanism of postsynaptic inhibition in frog spinal motoneurones was studied with conventional and with ion-sensitive microelectrodes. In these neurones the inhibitory postsynaptic ...potential was depolarizing, its reversal potential being 15 mV less negative than the resting membrane potential. During the inhibitory postsynaptic potential the input resistance of the motoneurones was reduced to 20% of the resting value, indicating a strong increase of membrane conductance. The Cl- equilibrium potential calculated from intra- and extracellular Cl- activity measurements coincided with the reversal potential of the inhibitory postsynaptic potential to within a few millivolts. During repetitive inhibitory postsynaptic activity the intracellular Cl- activity decreased markedly, while the extracellular Cl- activity increased slightly. These changes of intra- and extracellular Cl- activities were no longer found after suppression of the inhibitory postsynaptic potential by strychnine. Blockade of an active, inward-going Cl- transport system in motoneurones by NH+4 led to a shift of the Cl- equilibrium potential and the reversal potential of the inhibitory postsynaptic potential towards the resting membrane potential. After prolonged action of NH+4, the Cl- equilibrium potential approached the membrane potential to within 5 mV, while the reversal potential of the inhibitory postsynaptic potential and resting membrane potential coincided. The difference between Cl- equilibrium potential and membrane potential after blockade of the Cl- pump is traced back to interfering intracellular ions, such as HCO-3 or SO42-, leading to an overestimation of intracellular Cl- activity and to the calculation of an erroneous Cl- equilibrium potential. Inhibitory amino acids like gamma-aminobutyrate or beta-alanine evoked depolarizations with reversal potentials similar to that of the inhibitory postsynaptic potential. These depolarizations were associated with a marked decrease of neuronal input resistance during inhibition. During the actions of these compounds a decrease of intracellular and a small increase of extracellular Cl- activity were found. The activities of other ions (K+, Ca2+ and Na+) did not change significantly, with the exception of extracellular K+ activity, which was slightly increased. Evidence is presented that the inhibitory postsynaptic potential, as well as the depolarizing action of inhibitory amino acids in motoneurones, is the result of an increase in membrane Cl- permeability and an efflux of Cl- from these cells, while other ions do not seem to be involved.
Thin sections and freeze-fracture replicas were used to investigate the ultrastructural changes associated with renin secretion from the juxtaglomerular part of the afferent arteriole of male mice. ...Adrenalectomized animals in which renin secretion was stimulated by furosemide application and bleeding were also studied. Exocytosis of mature electron-dense granules was found in all experimental groups. Before extrusion, the region of granule facing the cell membrane changed, with vesicular and/or stacked membrane-like profiles and a small local protrusion of the granule membrane appearance of. Concomitantly, punctuate sites of fusion between the cell and granule membranes were observed. Later, unaltered amorphous, and altered membrane-like granule content was released from omega-shaped cavities into the extracellular space. In stimulated animals the alteration and extrusion of several closely apposed granules was reminiscent of compound exocytosis. Coated pits were frequently seen, suggesting specific retrieval of the former granule membrane. The collapsing silhouette of a depleted granule very rarely took the form of a saccule whose narrow membrane-bounded neck was continuous with the extracellular space. Observed were two additional events by which active and inactive renin may be released. Small electron-lucent vacuoles of undetermined origin fused with the cell membrane and, in stimulated kidneys, some epithelioid cell processes disintegrated. However, the interpretation of the related ultrastructural phenomena was uncertain.
Microelectrode recordings were performed in renin-containing epithelioid (JG) and vascular smooth muscle (VSM) cells of the afferent arteriole in the isolated hydronephrotic mouse kidney. Both cell ...types had a membrane potential of about -75 mV and exhibited small, spontaneous depolarizing transients, probably resulting from random transmitter release by sympathetic axon terminals. Substances depressing renin secretion, such as angiotensin II, arginine-vasopressin, and alpha 1-adrenergic agents reversibly depolarized both JG and VSM cells. On a molar basis, the action of angiotensin II was strongest. Stimulators of renin release, e.g. isoproterenol, histamine, and prostaglandin E2 did not influence the membrane potential of both cell types. VIP and NPY, possible co-transmitters of norepinephrine, as well as AP II, were also without effect. It is proposed that suppression of renin secretion from JG cells is mediated by depolarization and Ca2+ influx, whereas stimulation is triggered independently from membrane potential changes, e.g. by adenylate cyclase activation.
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