Adult hippocampal neurogenesis and its impairment in Alzheimer's disease.

Adult neurogenesis is the creation of new neurons which integrate into the existing neural circuit of the adult brain. Recent evidence suggests that adult hippocampal neurogenesis (AHN) persists throughout life in mammals, including humans. These newborn neurons have been implicated to have a crucial role in brain functions such as learning and memory. Importantly, studies have also found that hippocampal neurogenesis is impaired in neurodegenerative and neuropsychiatric diseases. Alzheimer's disease (AD) is one of the most common forms of dementia affecting millions of people. Cognitive dysfunction is a common symptom of AD patients and progressive memory loss has been attributed to the degeneration of the hippocampus. Therefore, there has been growing interest in identifying how hippocampal neurogenesis is affected in AD. However, the link between cognitive decline and changes in hippocampal neurogenesis in AD is poorly understood. In this review, we summarized the recent literature on AHN and its impairments in AD.

Integrating the Roles of Midbrain Dopamine Circuits in Behavior and Neuropsychiatric Disease.

Dopamine (DA) is a behaviorally and clinically diverse neuromodulator that controls CNS function. DA plays major roles in many behaviors including locomotion, learning, habit formation, perception, and memory processing. Reflecting this, DA dysregulation produces a wide variety of cognitive symptoms seen in neuropsychiatric diseases such as Parkinson's, Schizophrenia, addiction, and Alzheimer's disease. Here, we review recent advances in the DA systems neuroscience field and explore the advancing hypothesis that DA's behavioral function is linked to disease deficits in a neural circuit-dependent manner. We survey different brain areas including the basal ganglia's dorsomedial/dorsolateral striatum, the ventral striatum, the auditory striatum, and the hippocampus in rodent models. Each of these regions have different reported functions and, correspondingly, DA's reflecting role in each of these regions also has support for being different. We then focus on DA dysregulation states in Parkinson's disease, addiction, and Alzheimer's Disease, emphasizing how these afflictions are linked to different DA pathways. We draw upon ideas such as selective vulnerability and region-dependent physiology. These bodies of work suggest that different channels of DA may be dysregulated in different sets of disease. While these are great advances, the fine and definitive segregation of such pathways in behavior and disease remains to be seen. Future studies will be required to define DA's necessity and contribution to the functional plasticity of different striatal regions.

The interplay of neurovasculature and adult hippocampal neurogenesis.

The subgranular zone of the dentate gyrus provides a local microenvironment (niche) for neural stem cells. In the adult brain, it has been established that the vascular compartment of such niches has a significant role in regulating adult hippocampal neurogenesis. More recently, evidence showed that neurovascular coupling, the relationship between blood flow and neuronal activity, also regulates hippocampal neurogenesis. Here, we review the most recent articles on addressing the intricate relationship between neurovasculature and adult hippocampal neurogenesis and a novel pathway where functional hyperemia enhances hippocampal neurogenesis. In the end, we have further reviewed recent research showing that impaired neurovascular coupling may cause declined neurogenesis and contribute to brain damage in neurodegenerative diseases.

GluN2A NMDA Receptor Enhancement Improves Brain Oscillations, Synchrony, and Cognitive Functions in Dravet Syndrome and Alzheimer's Disease Models.

NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via allosteric modulation are largely unknown. We examine the in vivo effects of GNE-0723, a positive allosteric modulator of GluN2A-subunit-containing NMDARs, on brain network and cognitive functions in mouse models of Dravet syndrome (DS) and Alzheimer's disease (AD). GNE-0723 use dependently potentiates synaptic NMDA receptor currents and reduces brain oscillation power with a predominant effect on low-frequency (12-20 Hz) oscillations. Interestingly, DS and AD mouse models display aberrant low-frequency oscillatory power that is tightly correlated with network hypersynchrony. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in DS and AD mouse models. GluN2A-subunit-containing NMDAR enhancers may have therapeutic benefits in brain disorders with network hypersynchrony and cognitive impairments.

Predictive (subtle or overlooked) initial head CT findings in patients who develop delayed chronic subdural hematoma.

With the aging population, the incidence of chronic subdural hematoma (CSDH) is expected to rise. Once symptomatic the morbidity from CSDH is not insignificant. We studied patients who had a minor head injury and CT brain scan prior to developing CSDH to determine if there were any predictors on these scans for subsequent development of a CSDH. A retrospective review was performed on all patients operated for CSDH over a 3-year period and a review performed on those who had imaging studies at the time of a preceding minor head injury. Seven of 37 patients had CT scans prior to developing CSDH. All had evidence of small increases in CSF intensity on the side or sides of the subsequent CSDH. In conclusion, in those patients with a history of minor head injury prior to developing a CSDH, CT brain demonstrated small increases in cerebral spinal fluid (CSF) intensity on the side or sides of the subsequent CSDH. Recognizing this finding may be helpful in monitoring these patients or initiating medical therapy.

Peroneal intraneural ganglia: the importance of the articular branch. Clinical series.

OBJECT: The peroneal nerve is the most common site of intraneural ganglia. The neurological deficit associated with these cysts is often severe and the operation to eradicate them is difficult The aims of this multicenter study were to collate the authors' experience with a relatively rare lesion and to improve clinical outcomes by better understanding its controversial pathogenesis. METHODS: Part I of this paper offers a description of 24 patients with peroneal intraneural ganglia who were treated by surgeons aware of the importance of the peroneal nerve's articular branch. Part II offers a description of three more patients who were seen after earlier operations in which the ganglion was excised, but the articular branch was not identified (all reportedly gross-total resections). Twenty-six of the 27 patients presented with clinical electrophysiological, and imaging evidence of a common peroneal nerve (CPN) lesion, predominantly affecting the deep peroneal nerve (DPN) division, and one patient presented with a painful mass of the CPN that was not accompanied by a neurological deficit. In all 24 patients in Part I there was magnetic resonance (MR) imaging evidence of a connection between the cyst and the superior tibiofibular joint, including one patient in whom high-resolution (3-tesla) MR neurography demonstrated the pathological articular branch itself. At the operation, the communication proved to extend through the articular branch of the CPN in all cases. The operation consisted of drainage of the cyst and ligation of the articular branch. At a minimum follow-up period of 1 year, these patients experienced significant improvements in their neuropathic pain, but only mild improvements in their functional deficits. In none of the 24 patients was there evidence of an intraneural recurrence. In three patients, however, extraneural ganglia developed: two patients with symptoms subsequently underwent resection of the superior tibiofibular joint without further recurrence and one patient with no symptoms was followed clinically after the recurrence was detected incidentally on 1-year postoperative imaging. As predicted, in Part II all three patients in whom the articular branch had not been ligated experienced early intraneural recurrence; both postoperative MR images and original studies, which were retrospectively examined, demonstrated a connection with the superior tibiofibular joint. CONCLUSIONS: The clinical presentation, electrical studies, imaging characteristics, and operative observations regarding peroneal intraneural ganglia are predictable. Treatment must address the underlying pathoanatomy and should include decompression of the cyst and ligation of the articular branch of the nerve. To avoid extraneural recurrence, resection of the superior tibiofibular joint may also be necessary, but indications for this additional procedure need to be defined. These recommendations are based on the authors' belief that intraneural peroneal ganglia arise from the superior tibiofibular joint and are connected to it by the articular branch.