Anatomical Location of the Vesical Branches of the Inferior Hypogastric Plexus in Human Cadavers.

We have demonstrated in canines that somatic nerve transfer to vesical branches of the inferior hypogastric plexus (IHP) can be used for bladder reinnervation after spinal root injury. Yet, the complex anatomy of the IHP hinders the clinical application of this repair strategy. Here, using human cadavers, we clarify the spatial relationships of the vesical branches of the IHP and nearby pelvic ganglia, with the ureteral orifice of the bladder. Forty-four pelvic regions were examined in 30 human cadavers. Gross post-mortem and intra-operative approaches (open anterior abdominal, manual laparoscopic, and robot-assisted) were used. Nerve branch distances and diameters were measured after thorough visual inspection and gentle dissection, so as to not distort tissue. The IHP had between 1 to 4 vesical branches (2.33 ± 0.72, mean ± SD) with average diameters of 0.51 ± 0.06 mm. Vesical branches from the IHP arose from a grossly visible pelvic ganglion in 93% of cases (confirmed histologically). The pelvic ganglion was typically located 7.11 ± 6.11 mm posterolateral to the ureteral orifice in 69% of specimens. With this in-depth characterization, vesical branches from the IHP can be safely located both posterolateral to the ureteral orifice and emanating from a more proximal ganglionic enlargement during surgical procedures.

Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral and anal sphincter function. Part 4: Effectiveness of the motor reinnervation.

In pilot work, we showed that somatic nerve transfers can restore motor function in long-term decentralized dogs. We continue to explore the effectiveness of motor reinnervation in 30 female dogs. After anesthesia, 12 underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. Twelve months postdecentralization, eight underwent transfer of obturator nerve branches to pelvic nerve vesical branches, and sciatic nerve branches to pudendal nerves, followed by 10 mo recovery (ObNT-ScNT Reinn). The remaining four were euthanized 18 mo postdecentralization (Decentralized). Results were compared with 18 Controls. Squat-and-void postures were tracked during awake cystometry. None showed squat-and-void postures during the decentralization phase. Seven of eight ObNT-ScNT Reinn began showing such postures by 6 mo postreinnervation; one showed a return of defecation postures. Retrograde dyes were injected into the bladder and urethra 3 wk before euthanasia, at which point, roots and transferred nerves were electrically stimulated to evaluate motor function. Upon L2-L6 root stimulation, five of eight ObNT-ScNT Reinn showed elevated detrusor pressure and four showed elevated urethral pressure, compared with L7-S3 root stimulation. After stimulation of sciatic-to-pudendal transferred nerves, three of eight ObNT-ScNT Reinn showed elevated urethral pressure; all showed elevated anal sphincter pressure. Retrogradely labeled neurons were observed in L2-L6 ventral horns (in laminae VI, VIII, and IX) of ObNT-ScNT Reinn versus Controls in which labeled neurons were observed in L7-S3 ventral horns (in lamina VII). This data supports the use of nerve transfer techniques for the restoration of bladder function.NEW & NOTEWORTHY This data supports the use of nerve transfer techniques for the restoration of bladder function.

Supinator to Posterior Interosseous Nerve Transfer for Recovery of Hand Opening in the Tetraplegic Patient: A Case Series.

BACKGROUND AND OBJECTIVES: Cervical spinal cord injury results in devastating loss of function. Nerve transfers can restore functional use of the hand, the highest priority function in this population to gain independence. Transfer of radial nerve branches innervating the supinator to the posterior interosseous nerve (SUP-PIN) has become a primary intervention for the recovery of hand opening, but few outcome reports exist to date. We report single-surgeon outcomes for this procedure. METHODS: The SUP-PIN transfer was performed on adults with traumatic spinal cord injury resulting in hand paralysis. Outcome measures include Medical Research Council strength grade for extension of each digit, and angles representing critical apertures: the first web space opening of the thumb, and metacarpophalangeal angle of the remaining fingers. Factors affecting these measurements, including preserved tone and spasticity of related muscles, were also assessed. RESULTS: Twenty-three adult patients with a C5-7 motor level underwent SUP-PIN transfers on 36 limbs (median age 31 years, interquartile range [21.5, 41]). The median interval from injury to surgery was 10.5 (8.2, 6.5) months, with 9 (7.5, 11) months for the acute injuries and 50 (32, 66) months for the chronic (>18 months) injuries. Outcomes were observed at a mean follow-up of 22 (14, 32.5) months. 30 (83.3%) hands recovered at least antigravity extension of the thumb and 34 (94.4%) demonstrated successful antigravity strength for the finger extensors, providing adequate opening for a functional grasp. Chronic patients (>18 months after injury) showed similar outcomes to those who had earlier surgery. Supination remained strong (at least M4) in all but a single patient and no complications were observed. CONCLUSION: SUP-PIN is a reliable procedure for recovery of finger extension. Chronic patients remain good candidates, provided innervation of target muscles is preserved. Higher C5 injuries were more likely to have poor outcomes.

Selective Tibial Neurotomy for Spastic Equinovarus Foot: Operative Technique.

BACKGROUND AND OBJECTIVES: Spastic equinovarus foot (SEF) is a common complication of stroke and other upper motor neuron injuries. It is characterized by a plantigrade and inverted foot, often with toe curling, causing significant disability from pain, gait, and balance difficulties. Management includes physical therapy, antispasticity drugs, orthoses, chemical neurolysis, or botulinum toxin, all of which may be insufficient, sedating, or transient. Selective tibial neurotomy (STN) provides a surgical option that is effective and long-lasting. Our goal is to provide a concise description of our technique for performing the STN for treatment of SEF. We discuss the standard posterior approach with surgical variations used by other groups and a medial approach, should the posterior approach be insufficient. METHODS: A posterior leg approach allows access to the tibial nerve and its branches to the bilateral gastrocnemius muscles, soleus, posterior tibialis, and extrinsic toe flexors. A medial approach is used if the toe flexors cannot be accessed sufficiently from the posterior approach. Nerve branch targets identified by preoperative functional assessment are carefully exposed and fully neurolysed distally to identify all terminal branches to each muscle of interest before neurotomy. RESULTS: The STN is a powerful tool for treating SEF, with an immediate and lasting effect. Approximately 80% of the target muscle should be denervated to ensure long-term efficacy while maintaining adequate function of the muscle through collateral innervation. CONCLUSION: The STN is a safe and effective outpatient procedure that can be performed by an experienced nerve surgeon to improve balance and ambulation and reduce pain for patients with SEF. Large clinical trials are necessary to further establish this underutilized procedure in the United States.

Axillary to Radial Nerve Transfer for Recovery of Elbow Extension After Spinal Cord Injury.

BACKGROUND AND OBJECTIVES: Cervical spinal cord injuries (SCI) result in severe loss of function and independence. Nerve transfers have become a powerful method for restoring upper extremity function, the most critical missing function desired by this patient population. Recovery of active elbow extension allows for expansion of one's workspace to reach for objects and stabilizes control at the elbow joint. Without triceps function, a patient with a cervical SCI is rendered entirely helpless when in the supine position. Our objective was to provide a concise description of the transfer of branches of the axillary nerve (AN) to the long head of the triceps branch of the radial nerve (RN) for restoration of elbow extension after cervical SCI. METHODS: An anterior, axillary approach is used for the transfer of the nerve branches of the AN (which may include branches to the teres minor, posterior deltoid, or even middle deltoid) to the long head of the triceps branch of the RN. Preoperative assessment and intraoperative stimulation are demonstrated to direct optimal selection of axillary branch donors. RESULTS: The axillary approach provides full access to all branches of the AN in optimal proximity to triceps branches of the RN and allows for tension-free coaptation to achieve successful recovery of elbow extension. Final outcomes may not be achieved for 18 months. Of our last 20 patients with greater than 12-month follow-up, 13 have achieved antigravity strength in elbow extension, 4 are demonstrating ongoing progression, and 3 are definitive failures by 18 months. CONCLUSION: The axillary to RN transfer is an important intervention for recovery of elbow extension after cervical SCI, which significantly improves quality of life in this patient population. Further large population outcomes studies are necessary to further establish efficacy and increase awareness of these procedures.

Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cells.

Adult tissue stem cells contribute to tissue homeostasis and repair but the long-lived neurons in the human adult cerebral cortex are not replaced, despite evidence for a limited regenerative response. However, the adult cortex contains a population of proliferating oligodendrocyte progenitor cells (OPCs). We examined the capacity of rat cortical OPCs to be re-specified to a neuronal lineage both in vitro and in vivo. Expressing the developmental transcription factor Neurogenin2 (Ngn2) in OPCs isolated from adult rat cortex resulted in their expression of early neuronal lineage markers and genes while downregulating expression of OPC markers and genes. Ngn2 induced progression through a neuronal lineage to express mature neuronal markers and functional activity as glutamatergic neurons. In vivo retroviral gene delivery of Ngn2 to naive adult rat cortex ensured restricted targeting to proliferating OPCs. Ngn2 expression in OPCs resulted in their lineage re-specification and transition through an immature neuronal morphology into mature pyramidal cortical neurons with spiny dendrites, axons, synaptic contacts, and subtype specification matching local cytoarchitecture. Lineage re-specification of rat cortical OPCs occurred without prior injury, demonstrating these glial progenitor cells need not be put into a reactive state to achieve lineage reprogramming. These results show it may be feasible to precisely engineer additional neurons directly in adult cerebral cortex for experimental study or potentially for therapeutic use to modify dysfunctional or damaged circuitry.

Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral, and anal sphincter function in a dog model. Part 3. nicotinic receptor characterization.

Very little is known about the physiological role of nicotinic receptors in canine bladders, although functional nicotinic receptors have been reported in bladders of many species. Utilizing in vitro methods, we evaluated nicotinic receptors mediating bladder function in dogs: control (9 female and 11 male normal controls, 5 sham operated), Decentralized (9 females, decentralized 6-21 mo), and obturator-to-pelvic nerve transfer reinnervated (ObNT-Reinn; 9 females; decentralized 9-13 mo, then reinnervated with 8-12 mo recovery). Muscle strips were collected, mucosa-denuded, and mounted in muscle baths before incubation with neurotransmitter antagonists, and contractions to the nicotinic receptor agonist epibatidine were determined. Strip response to epibatidine, expressed as percent potassium chloride, was similar (∼35% in controls, 30% in Decentralized, and 24% in ObNT-Reinn). Differentially, epibatidine responses in Decentralized and ObNT-Reinn bladder strips were lower than controls after tetrodotoxin (TTX, a sodium channel blocker that inhibits axonal action potentials). Yet, in all groups, epibatidine-induced strip contractions were similarly inhibited by mecamylamine and hexamethonium (ganglionic nicotinic receptor antagonists), SR 16584 (α3ß4 neuronal nicotinic receptor antagonist), atracurium and tubocurarine (neuromuscular nicotinic receptor antagonists), and atropine (muscarinic receptor antagonist), indicating that nicotinic receptors (particularly α3ß4 subtypes), neuromuscular and muscarinic receptors play roles in bladder contractility. In control bladder strips, since tetrodotoxin did not inhibit epibatidine contractions, nicotinic receptors are likely located on nerve terminals. The tetrodotoxin inhibition of epibatidine-induced contractions in Decentralized and ObNT-Reinn suggests a relocation of nicotinic receptors from nerve terminals to more distant axonal sites, perhaps as a compensatory mechanism to recover bladder function.

A scoping review of current and emerging techniques for evaluation of peripheral nerve health, degeneration and regeneration: part 2, non-invasive imaging.

Peripheral neuroregenerative research and therapeutic options are expanding exponentially. With this expansion comes an increasing need to reliably evaluate and quantify nerve health. Valid and responsive measures of the nerve status are essential for both clinical and research purposes for diagnosis, longitudinal follow-up, and monitoring the impact of any intervention. Furthermore, novel biomarkers can elucidate regenerative mechanisms and open new avenues for research. Without such measures, clinical decision-making is impaired, and research becomes more costly, time-consuming, and sometimes infeasible. Part 1 of this two-part scoping review focused on neurophysiology. In part 2, we identify and critically examine many current and emerging non-invasive imaging techniques that have the potential to evaluate peripheral nerve health, particularly from the perspective of regenerative therapies and research.

A scoping review of current and emerging techniques for evaluation of peripheral nerve health, degeneration, and regeneration: part 1, neurophysiology.

Peripheral neuroregeneration research and therapeutic options are expanding exponentially. With this expansion comes an increasing need to reliably evaluate and quantify nerve health. Valid and responsive measures that can serve as biomarkers of the nerve status are essential for both clinical and research purposes for diagnosis, longitudinal follow-up, and monitoring the impact of any intervention. Furthermore, such biomarkers can elucidate regeneration mechanisms and open new avenues for research. Without these measures, clinical decision-making falls short, and research becomes more costly, time-consuming, and sometimes infeasible. As a companion to Part 2, which is focused on non-invasive imaging, Part 1 of this two-part scoping review systematically identifies and critically examines many current and emerging neurophysiological techniques that have the potential to evaluate peripheral nerve health, particularly from the perspective of regenerative therapies and research.

Selective Tibial Neurotomy Outcomes for Spastic Equinovarus Foot: Patient Expectations and Functional Assessment.

BACKGROUND: Spastic equinovarus foot (SEF) is a common dysfunctional foot posture after stroke that impairs balance and mobility. Selective tibial neurotomy (STN) is a simple but underutilized surgical option that can effectively address critical aspects of SEF and thereby provide enduring quality of life gains. There are few studies that examine both functional outcomes and patient satisfaction with this treatment option. OBJECTIVE: To elucidate the patient goals that motivated their decision to undergo the procedure and compare subjective and objective changes in balance and functional mobility as a consequence of surgery. METHODS: Thirteen patients with problematic SEF who had previously failed conservative measures were treated with STN. Preoperative and postoperative (on average 6 months) assessments evaluated gait quality and functional mobility. In addition, a custom survey was conducted to investigate patient perspectives on STN intervention. RESULTS: The survey showed that participants who opted for STN were dissatisfied with their previous spasticity management. The most common preoperative expectation for STN treatment was to improve walking, followed by improving balance, brace comfort, pain, and tone. Postoperatively, participants rated the improvement in their expectations and were, on average, 71 on a 100-point scale, indicating high satisfaction. The gait quality, assessed with the Gait Intervention and Assessment Tool, improved significantly between preoperative and postoperative assessment (M = -4.1, P = .01) with a higher average difference in stance of -3.3 than in swing -0.5. Improvement in both gait endurance (M = 36 m, P = .01) and self-selected gait speed (M = .12 m/s, P = .03) was statistically significant. Finally, static balance (M = 5.0, P = .03) and dynamic balance (M = 3.5, P = .02) were also significantly improved. CONCLUSION: STN improved gait quality and functional mobility and was associated with high satisfaction in patients with SEF.

Restoring bladder function using motor and sensory nerve transfers: a cadaveric feasibility study.

OBJECTIVE: Bladder dysfunction after nerve injury has a variable presentation, and extent of injury determines whether the bladder is spastic or atonic. The authors have proposed a series of 3 nerve transfers for functional innervation of the detrusor muscle and external urethral sphincter, along with sensory innervation to the genital dermatome. These transfers are applicable to only cases with low spinal segment injuries (sacral nerve root function is lost) and largely preserved lumbar function. Transfer of the posterior branch of the obturator nerve to the vesical branch of the pelvic nerve provides a feasible mechanism for patients to initiate detrusor contraction by thigh adduction. External urethra innervation (motor and sensory) may be accomplished by transfer of the vastus medialis nerve to the pudendal nerve. The sensory component of the pudendal nerve to the genitalia may be further enhanced by transfer of the saphenous nerve (sensory) to the pudendal nerve. The main limitations of coapting the nerve donors to their intrapelvic targets are the bifurcation or arborization points of the parent nerve. To ensure that the donor nerves had sufficient length and diameter, the authors sought to measure these parameters. METHODS: Twenty-six pelvic and anterior thigh regions were dissected in 13 female cadavers. After the graft and donor sites were clearly exposed and the branches identified, the donor nerves were cut at suitable distal sites and then moved into the pelvis for tensionless anastomosis. Diameters were measured with calipers. RESULTS: The obturator nerve was bifurcated a mean ± SD (range) of 5.5 ± 1.7 (2.0-9.0) cm proximal to the entrance of the obturator foramen. In every cadaver, the authors were able to bring the posterior division of the obturator nerve to the vesical branch of the pelvic nerve (located internal to the ischial spine) in a tensionless manner with an excess obturator nerve length of 2.0 ± 1.2 (0.0-5.0) cm. The distance between the femoral nerve arborization and the anterior superior iliac spine was 9.3 ± 1.8 (6.5-15.0) cm, and the distance from the femoral arborization to the ischial spine was 12.9 ± 1.4 (10.0-16.0) cm. Diameters were similar between donor and recipient nerves. CONCLUSIONS: The chosen donor nerves were long enough and of sufficient caliber for the proposed nerve transfers and tensionless anastomosis.

Spinal motor neuron transplantation to enhance nerve reconstruction strategies: Towards a cell therapy.

Nerve transfers have become a powerful intervention to restore function following devastating paralyzing injuries. A major limitation to peripheral nerve repair and reconstructive strategies is the progressive, fibrotic degeneration of the distal nerve and denervated muscle, eventually precluding recovery of these targets and thus defining a time window within which reinnervation must occur. One proven strategy in the clinic has been the sacrifice and transfer of an adjacent distal motor nerve to provide axons to occupy, and thus preserve (or "babysit"), the target muscle. However, available nearby nerves are limited in severe brachial plexus or spinal cord injury. An alternative and novel proposition is the transplantation of spinal motor neurons (SMNs) derived from human induced pluripotent stem cells (iPSCs) into the target nerve to extend their axons to occupy and preserve the targets. These cells could potentially be delivered through minimally invasive or percutaneous techniques. Several reports have demonstrated survival, functional innervation, and muscular preservation following transplantation of SMNs into rodent nerves. Advances in the generation, culture, and differentiation of human iPSCs now offer the possibility for an unlimited supply of clinical grade SMNs. This review will discuss the previous reports of peripheral SMN transplantation, outline key considerations, and propose next steps towards advancing this approach to clinic. Stem cells have garnered great enthusiasm for their potential to revolutionize medicine. However, this excitement has often led to premature clinical studies with ill-defined cell products and mechanisms of action, particularly in spinal cord injury. We believe the peripheral transplantation of a defined SMN population to address neuromuscular degeneration will be transformative in augmenting current reconstructive strategies. By thus removing the current barriers of time and distance, this strategy would dramatically enhance the potential for reconstruction and functional recovery in otherwise hopeless paralyzing injuries. Furthermore, this strategy may be used as a permanent axon replacement following destruction of lower motor neurons and would enable exogenous stimulation options, such as pacing of transplanted SMN axons in the phrenic nerve to avoid mechanical ventilation in high cervical cord injury or amyotrophic lateral sclerosis.

Supinator to Posterior Interosseous Nerve Transfer for Restoration of Finger Extension.

BACKGROUND: Cervical spinal cord injuries result in a severe loss of function and independence. The primary goal for these patients is the restoration of hand function. Nerve transfers have recently become a powerful intervention to restore the ability to grasp and release objects. The supinator muscle, although a suboptimal tendon transfer donor, serves as an ideal distal nerve donor for reconstructive strategies of the hand. This transfer is also applicable to lower brachial plexus injuries. OBJECTIVE: To describe the supinator to posterior interosseous nerve transfer with the goal of restoring finger extension following spinal cord or lower brachial plexus injury. METHODS: Nerve branches to the supinator muscle are transferred to the posterior interosseous nerve supplying the finger extensor muscles in the forearm. RESULTS: The supinator to posterior interosseous nerve transfer is effective in restoring finger extension following spinal cord or lower brachial plexus injury. CONCLUSION: This procedure represents an optimal nerve transfer as the donor nerve is adjacent to the target nerve and its associated muscles. The supinator muscle is innervated by the C5-6 nerve roots and is often available in cases of cervical SCI and injuries of the lower brachial plexus. Additionally, supination function is retained by supination action of the biceps muscle.

Falcine chondroma: illustrative case.

BACKGROUND: Chondromas are benign cartilaginous tumors that are rarely seen in the brain. OBSERVATIONS: A 58-year-old woman had undergone routine brain imaging after a motor vehicle accident and was incidentally found to have a right falcine lesion. Contrast magnetic resonance imaging showed a mostly nonenhancing mass with discontinuous rim enhancement. She was taken to the operating room and pathology revealed a chondroma. LESSONS: Falcine intracranial chondromas are rare and typically misdiagnosed as meningiomas. Chondromas should be in the differential for patients presenting with nonenhancing falcine lesions.

The evolution of nerve transfers for spinal cord injury.

Spinal cord injury (SCI) often results in devastating effects on function and quality of life. The majority of SCIs occur in the cervical region with restoration of arm and hand function being the highest priority by patients. Current restoration strategies rely on maximizing and optimally redistributing residual muscle functions that remain under volitional control. The polio epidemic and World Wars led to the development and refinement of tendon transfers, which has long been the standard reconstructive approach for the upper extremity following SCI. However, the past few decades has seen the emergence of nerve transfers from a "salvage" procedure for the management of peripheral nerve injuries, to a powerful reconstructive tool following SCI. Nerve transfers offer distinct advantages over tendon transfers; however, optimal functional recovery frequently benefits from a multi-modality approach and must be tailored to specific injury patterns. Extension of nerve transfers to the lower body presents additional hurdles such as limited donor nerve sources and much longer target distances. In this review, we will discuss the evolution of nerve transfers for upper extremity reanimation following cervical SCI and discuss advantages over tendon transfers. We will address the progress for nerve transfers to restore lower body function, including ambulation and bladder control. Finally, we will address future efforts in the field. Reconstructive modalities, including nerve and tendon transfers, remain underutilized following SCI and it is important that these therapeutic options are made known to the research community, medical providers, and patients.

Cyclophilin-D: a resident regulator of mitochondrial gene expression.

Cyclophilin-D (Cyp-D) is a mitochondrial matrix peptidyl-prolyl isomerase. Because cyclophilins can regulate nuclear gene expression, we examined whether Cyp-D could regulate mitochondrial gene expression. We demonstrated in HEK 293T cells that transfected Cyp-D interacts with mitochondrial transcription factors B1 and B2 (TFB2M) but not with mitochondrial transcription factor A. We also demonstrated that Cyp-D interacts in vivo with TFB2M. Genetic silencing of Cyp-D and pharmacologic inhibition of Cyp-D markedly reduced mitochondrial transcription to 18 ± 5% (P < 0.05) and 24 ± 3% (P < 0.05) of respective controls. The level of interaction between Cyp-D and TFB2M correlated with the level of nascent mitochondrial RNA intensity (r = 0.896; P = 0.0156). Cyp-D silencing down-regulated mitochondrial transcripts initiated from the heavy strand promoter 2 [i.e., NADH dehydrogenase 1 (ND1) by 11-fold, P < 0.005; cytochrome oxidase 1 (COX1) by 4-fold, P < 0.001; and ATP synthase subunit 6 (ATP6) by 6.5-fold, P < 0.005); but not NADH dehydrogenase 6 (ND6)], which is initiated from the light strand promoter. Cyp-D silencing reduced mitochondrial membrane potential and cellular oxygen consumption (from 59 ± 5 to 34 ± 1 µmol oxygen/min/10(6) cells, P < 0.001); the latter without a statistically significant reversal after uncoupling electron transport from ATP synthesis, consistent with down-regulation of electron transport complexes. Accordingly, these studies provide novel evidence that Cyp-D could play a key role in regulating mitochondrial gene expression.

Prospects for engineering neurons from local neocortical cell populations as cell-mediated therapy for neurological disorders.

There is little cell replacement following neurological injury, limiting the regenerative response of the CNS. Progress in understanding the biology of neural stem cells has raised interest in using stem cells for replacing neurons lost to injury or to disease. Stem cell therapy may also have a role in rebuilding deficient neural circuitry underlying mood disorders, epilepsy, and pain modulation among other roles. In vitro expansion of stem cells with directed differentiation prior to transplantation is one approach to stem cell therapy. Emerging evidence suggests that it may be possible to convert in vivo endogenous neural cells to a neuronal fate directly, providing an alternative strategy for stem cell therapy to the CNS. This review assesses the evidence for engineering a subtype-specific neuronal fate of endogenous neural cells in the cerebral cortex as a function of initial cell lineage, reactive response to injury, conversion factors, and environmental context. We conclude with a discussion of some of the challenges that must be overcome to move this alternative in vivo engineered conversion process toward becoming a viable therapeutic option.

Investigation of antimicrobial and protease-inhibitory activity from cultured cyanobacteria.

A culture collection of cyanobacteria has been established at the University of Illinois at Chicago. This collection includes marine, terrestrial, and freshwater strains and contains representatives of the five orders of cyanobacteria: Chroococcales, Pleurocapsales, Oscillatoriales, Nostocales, and Stigonematales. In this study, extracts from a subset of 61 strains, 16 marine and 45 freshwater/terrestrial, were evaluated against three current protease targets, i.e. 20S proteasome and two SARS viral proteases, two important bacterial targets, i.e. Mycobacterium tuberculosis and Bacillus anthracis, and in the Artemia salina toxicity assay. In total, extracts of 12 strains possessed significant levels of activity in one or more targets. The overwhelming majority of active extracts (11 of 12) were from either freshwater or terrestrial forms of cyanobacteria, with the greater part of these (9 of 12) being heterocyst-forming strains. These results further support the use of cultured cyanobacteria as a source of biologically active natural products.