Neurodegenerative diseases (NDDs), including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and Huntington’s Disease (HD), share pathologic mechanisms including oxidative stress, mitochondrial dysfunction, and protein aggregation. However, they differ in age of onset and clinical progression. Emerging evidence highlights primary cilia (PC) as a key regulator of neuronal aging and the progression of these diseases. Dysfunctional PC may impair key signaling pathways, such as Sonic Hedgehog (Shh) and Wnt, promote oxidative stress, mitochondrial damage, and epigenetic instability. PC may also influence intercellular communication by regulating the biogenesis of exosomes and modulating tunneling nanotube (TNT) formation, both of which propagate toxic proteins between neurons. Mechanistically, the regulation of ciliary length is disrupted in AD, which leads to ciliary dysfunction that interferes with signaling pathways and promotes the aggregation of amyloid-beta. This amyloid-beta is then propagated through TNTs and exosomes, spreading neuronal damage. In PD, the accumulation of alpha-synuclein (α-syn) also impairs cilia function, thereby compromising the cell’s response to oxidative stress. This results in the formation of abnormal TNTs and defective exosome-mediated clearance, ultimately contributing to neurodegeneration. Similarly, the mutant huntingtin protein aggregates within primary cilia in HD, morphologically disrupting them by obstructing intraflagellar transport. Damaged cilia are also associated with increased TNT formation and the exosomal release of toxic proteins, which leads to mitochondrial and epigenetic instability, ultimately promoting neuronal aging. Together, targeting ciliary function and its downstream regulation of TNTs and exosomes may provide a novel approach for slowing or halting disease progression across neurodegenerative diseases.

Accurate identification of the epidural space is critical for procedures such as labor analgesia, postoperative pain management, and epidural steroid injections. The current loss-of-resistance (LOR) technique depends on subtle tactile cues, which are highly subjective and prone to variability and complications. The objective was to develop and evaluate a prototype device (EpiduraFlow) that provides real-time quantitative feedback using pressure and flow metrics to enhance the accuracy and reliability of epidural space identification. A prototype system was designed incorporating a piezoelectric micropump, differential pressure sensors, and a microcontroller with LCD display. The device infused saline at a controlled rate through a Tuohy epidural needle, continuously recording flow and pressure. Testing was performed on a validated epidural simulation model at the UCSD Health SimCenter. Flow and pressure changes were analyzed during needle advancement across simulated tissue layers. Mean flow rate during advancement through simulated soft tissue and ligamentous layers was 1.02 ± 0.84 µL/s, compared with 29.7 ± 5.3 µL/s upon entry into the simulated epidural space (p << 0.001). Pressure dropped correspondingly at the moment of entry, and changes were displayed in real time on the LCD. Calibration of sensors against a manometer demonstrated high linearity (R² > 0.98). EpiduraFlow reliably identified transitions into the epidural space during simulated procedures. This proof-of-concept demonstrates the feasibility of objective, quantitative epidural localization and supports further development toward handheld, sterile-compatible designs and preclinical validation.