We have investigated the possible roles of NGF, and of impulse activity, in the regeneration of sensory nerves. Unexpectedly, the ability of crushed axons to regrow and to restore functional recovery of three sensory modalities in adult rat skin (A alpha-mediated touch, A delta-mediated mechanonociception, and C-fiber-mediated heat nociception) was totally unaffected by anti-NGF treatment. This finding applied even when the anti-NGF dosage was almost eight times that which entirely blocked collateral sprouting of the undamaged axons of both classes of nociceptive nerves (the A alpha-axons do not sprout in adult animals). In the same anti-NGF-treated animal, regeneration would proceed normally on the one side, while collateral sprouting was prevented on the other. Light microscopic and EM examination revealed that in the denervated skin the regenerating axons utilized the same dermal perineurial pathways followed by collaterally sprouting axons. Regeneration within these antibody-accessible pathways progressed normally during anti-NGF treatment, extending 1-2 cm beyond the former field borders, that is, into territory whose invasion by collaterally sprouting axons was totally blocked. The blood-nerve barrier is absent within the degenerating peripheral nerve trunk, a putative NGF source for regenerating fibers but not for sprouting ones. The NGF-independent regeneration was also found to be unaffected when putative spinal cord sources of NGF were eliminated by dorsal root excision. Anti-NGF treatment also failed to block regeneration across 4 mm excision gaps in the nerve trunk. The daily anti-NGF regime continued to be effective for at least 8 weeks, at which time newly evoked collateral sprouting could still be blocked. Exogenous NGF, in doses that evoke collateral sprouting de novo in normal skin, failed to influence regeneration. Finally, an electrical stimulus regime, which markedly reduces the latency of collateral sprouting, failed to affect the time to arrival of regenerating axons at the skin, or the rate of their arborization in it. We conclude that, in striking contrast to their collateral sprouting, the regeneration of nociceptive axons occurs independently of endogenous NGF and is unaffected by impulse activity. These findings further support the proposal that these two growth behaviors have basically different biological functions in the organism.

Lesions with precisely defined boundaries were made, in adult rat brains, with a new type of cutting device that remained implanted during various survival times. The subsequent events were followed histologically in silver-stained (including Fink-Heimer) horizontal sections, with myelin and nuclear counterstains. The devices, inserted vertically through the dorsal surface of the brain until they met the floor of the skull, consisted of a horizontal cutting wire (0.9--2.6 mm long) between two vertical support wires, all 90 micrometers diameter. Following fixation of the brain, the device was removed from its ventral surface; thus, the channels left by the support wires appeared as two holes in horizontal sections, clearly marking the limits of the cut. The extents of the tissue cut by, and that passively deflected around, such devices were characterized from mearsurements of brains examined immediately after an incision was made and from degeneration studies after 3-day implantations. After implantations of 18--230 days, the severed axons no longer abutted the line of such lesions, as seen initially; now axons were often observed to extend alongside the lesion, then to bend and course around the support wire. Such "detours' ' curved back into the injured tracts, seeming to reconnect them appropriately. Detours had begun by 3--8 days, and end-swellings were frequently seen on their reoriented axons. Neither collateral sprouting of spared axons nor passive deformation of brain tissue was consistent with the findings. It is concluded that a massive and reconstructive regeneration of cut axons occurred around the ends of lesions made by the cutting devices.

BackgroundSolid bio-wastes (or organic residues) are worldwide produced in high amount and increasingly considered bioenergy containers rather than waste products. A complete bioprocess from recalcitrant solid wastes to methane (SW2M) via anaerobic digestion (AD) is believed to be a sustainable way to utilize solid bio-wastes. However, the complex and recalcitrance of these organic solids make the hydrolysis process inefficient and thus a rate-limiting step to many AD technologies. Effort has been made to enhance the hydrolysis efficiency, but a comprehensive assessment over a complete flow scheme of SW2M is rare.ResultsIn this study, it comes to reality of a complete scheme for SW2M. A novel process to efficiently convert organic residues into methane is proposed, which proved to be more favorable compared to conventional methods. Brewers’ spent grain (BSG) and pig manure (PM) were used to test the feasibility and efficiency. BSG and PM were enzymatically pre-hydrolyzed and solubilized, after which the hydrolysates were anaerobically digested using different bioreactor designs, including expanded granular sludge bed (EGSB), continuously stirred tank reactor (CSTR), and sequencing batch reactor (SBR). High organic loading rates (OLRs), reaching 19 and 21 kgCOD · m−3 · day−1 were achieved for the EGSBs, fed with BSG and PM, respectively, which were five to seven times higher than those obtained with direct digestion of the raw materials via CSTR or SBR. About 56% and 45% organic proportion of the BSG and PM can be eventually converted to methane.ConclusionsThis study proves that complex organic solids, such as cellulose, hemicellulose, proteins, and lipids can be efficiently hydrolyzed, yielding easy biodegradable/bio-convertible influents for the subsequent anaerobic digestion step. Although the economical advantage might not be clear, the current approach represents an efficient way for industrial-scale treatment of organic residues with a small footprint and fast conversion of AD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13068-015-0237-8) contains supplementary material, which is available to authorized users.

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