Cortical Wound Research Articles

Rapid and Eco‐Friendly Preparation of Antibacterial Gauze by Alkali‐Acid Redeposition of Quercetin on Gauze Fiber and Subsequent Ultraviolet‐Assisted Reduction of Silver In Situ

AbstractRapid and eco‐friendly preparation of biomedical materials is significant for practical applications. This study proposes a simple two‐step method for preparing silver nanoparticles (AgNPs)‐functionalized gauze dressings (Ag‐Q‐G) with antibacterial activity in a green and time‐efficient manner that requires <10 min. A smooth and uniform quercetin coating is formed on the gauze fibers using alkali–acid redeposition for 10 s. Subsequently, AgNPs are rapidly formed (in 5 min) and firmly deposited on the quercetin‐coated gauze by ultraviolet irradiation in an AgNO3 solution. The in vitro results indicate that Ag–Q–G exhibits excellent antibacterial activity, with a rate of 99.57% ± 0.52% against Staphylococcus aureus and 95.59% ± 1.50% against Escherichia coli, while maintaining acceptable cytocompatibility. An animal study reveals that Ag‐Q‐G reduces infection and promotes wound healing in a rat dorsal total cortical wound model. This approach provides a practical option for the commercial production of antibacterial gauze dressings.

Evaluation of the safety of retroperitoneal laparoscopic partial nephrectomy by investigating the perioperative indicators.

In recent years, open nephron sparing partial nephrectomy (OPN) has been gradually applied and generally accepted. Recent statistical data show that PN not only can safely and effectively preserve the functional nephron, but also has fewer complications, low local recurrence rate and no significant difference in long-term survival rate compared with nephrectomy/radical nephrectomy, which has gradually become a routine treatment for small renal cell carcinoma. Therefore, how to maximize the protection of postoperative residual renal function (RRF) and reduce the risk of CKD while achieving the ideal local and overall tumor control effect is the key to the treatment of renal cancer, and is also the focus of attention of urologists and nephrologists. To evaluate the safety of retroperitoneal laparoscopic partial nephrectomy (RLPN) by investigating the perioperative indicators and postoperative follow-up. A total of 40 hospitalized patients in our hospital from December 2019 to December 2021 were selected and followed up for a long time. Patients with renal tumors less than 4cm in diameter and exogeneous or partial exogeneity were randomly divided into 2 groups. Patients in retroperitoneal laparoscopic group (n = 20) were treated with nephron sparing partial nephrectomy (0.5-1cm). Twenty patients underwent retroperitoneal laparoscopic radical nephrectomy (LRN).The time of removal of drainage tube, drainage volume, time of feeding activity and postoperative hospital stay were recorded, and the safety of the operation was evaluated. nephron sparing partial nephrectomy is suitable for patients with localized renal carcinoma or benign tumor <4cm. RLPN can be applied to all indications of open nephron sparing partial nephrectomy (OPN), with good safety, and can preserve residual renal function to the greatest extent. The operative vascular occlusion time was controlled within 40 minutes, and the use of renal function protection measures during the operation was safe and controllable in reducing the prevention of warm ischemic kidney damage, with good safety. The renal tumor capsule with 0.5cm~1cm margin was complete by postoperative pathology. In the process of tumor resection and suture collection system in the RLPN group, we improved the previous operation of "resection before hemostasis" to "resection while hemostasis" and "knot-free suture" technology, which saved the operation time of intracavity suture knotting. Reduced cortical tear caused by vertical pull during knot tying. The combined effect of biological clip and hemostatic gauze can stimulate the granulation proliferation of renal cortical wound and accelerate the repair. With the combination of knot-free suture and renal segment vascular occlusion, hot ischemic kidney damage is reduced. In the RLPN group, there were no complications of urinary fistula and bleeding, and no abnormal changes in renal function during follow-up. The safety of RLPN group is worthy of affirmation. The perioperative safety and short-term postoperative renal function recovery of RLPN are good, and the overall safety of this operation is worthy of affirmation.

Marmoset model of trauma-induced epileptogenesis

We investigated brain electrographic activity in freely behaving marmosets before and after cortical penetrating wound. Based on visual examination of the multi-channel cortical and hippocampal LFP recordings and muscle activity, we were able to distinguish six behavioural states: active and quiet wake, an intermediate state, NREM2, SWS and REM sleep. We developed a procedure for automatic classification of states of vigilance in marmosets based on different LFP power bands and muscle tone with the use of self-organizing maps. Marmosets were typically awake during the day with few occasional naps and had 12–18 sleep cycles during night. In order to evaluate them as a model of human trauma-induced epileptogenesis, we produced cortical penetrating wound in 3 marmosets. All of them developed electrographic epileptiform activity within the first weeks that was primarily local. Its secondary generalization led to behavioural seizures that started to manifest 2–4 weeks after the onset of electrographic events. Conclusion: Cortical penetrating wounds in marmosets trigger epileptogenesis that result in seizure onset within a few weeks. Their brain state cycle is closer to human as compared to typical laboratory animals (rodents and carnivores) that favours translation of findings in marmoset model of trauma-induced epileptogenesis to human studies. Supported by CIHR and Savoy Foundation.

Age dependency of trauma-induced neocortical epileptogenesis.

Trauma and brain infection are the primary sources of acquired epilepsy, which can occur at any age and may account for a high incidence of epilepsy in developing countries. We have explored the hypothesis that penetrating cortical wounds cause deafferentation of the neocortex, which triggers homeostatic plasticity and lead to epileptogenesis (Houweling etal., 2005). In partial deafferentation experiments of adult cats, acute seizures occurred in most preparations and chronic seizures occurred weeks to months after the operation in 65% of the animals (Nita etal., 2006,2007; Nita and Timofeev, 2007). Similar deafferentation of young cats (age 8–12 months) led to some acute seizures, but we never observed chronic seizure activity even though there was enhanced slow-wave activity in the partially deafferented hemisphere during quiet wakefulness. This suggests that despite a major trauma, the homeostatic plasticity in young animals was able to restore normal levels of cortical excitability, but in fully adult cats the mechanisms underlying homeostatic plasticity may lead to an unstable cortical state. To test this hypothesis we made an undercut in the cortex of an elderly cat. After several weeks this animal developed seizure activity. These observations may lead to an intervention after brain trauma that prevents epileptogenesis from occurring in adults.

Evaluation of injectable silica-embedded nanohydroxyapatite bone substitute in a rat tibia defect model

In clinical practice, vertebral compression fractures occur after trauma and osteoporosis. Kyphoplasty is a minimally invasive procedure using bone filler material for the treatment of such fractures. A full synthetic injectable bone substitute (SIBS) was manufactured by means of spray drying. The aim of this study was to characterize the SIBS and to analyze the remodelling process during degradation of the biomaterial and new bone formation after implantation. SIBS is an aqueous suspension of donut-like microparticles. These microparticles consist of nanocrystallites of synthetic hydroxyapatite embedded in amorphous silica gel. After implantation of SIBS in a proximal tibial diaphyseal defect in 52 rats, grafts were harvested for subsequent analysis on different days. Newly formed bone originating from endosteum was observed on day 6. Hematomas in the medullary space and cortical wounds disappeared on day 12. The wound region was completely replaced by a composite of newly formed cancellous bone, extracellular matrix, and SIBS. At day 63 the cortical defect was fully healed by bone, while newly formed bone in the medullary space almost disappeared and was replaced with bone marrow. In conclusion, SIBS demonstrated a unique structure with osteoinductive and bioresorbable properties, which induced fast bone regeneration. Therefore, a clinical application of SIBS for kyphoplasty is promising.

Neocortical Post-Traumatic Epileptogenesis Is Associated with Loss of GABAergic Neurons

The subtle mechanisms of post-traumatic epileptogenesis remain unknown, although the incidence of chronic epilepsy after penetrating cortical wounds is high. Here, we investigated whether the increased frequency of seizures occurring within 6 weeks following partial deafferentation of the suprasylvian gyrus in cats is accompanied with a change in the ratio between the number of excitatory and inhibitory neurons. Immuno-histochemical labeling of all neurons with neuronal-specific nuclear protein (NeuN) antibody, and of the GABAergic inhibitory neurons with either gamma-aminobutyric acid (GABA) or glutamic acid decarboxylase (GAD 65&67) antibodies, was performed on sections obtained from control and epileptic animals with chronically deafferented suprasylvian gyrus. Quantification of the labeled neurons was performed in control animals and at 2, 4, and 6 weeks following cortical deafferentation, in the suprasylvian and marginal gyri, both ipsi- and contra-lateral to the cortical trauma. In all epileptic animals, the neuronal loss was circumscribed to the deafferented suprasylvian gyrus. Inhibitory GABAergic neurons were particularly more sensitive to cortical deafferentation than excitatory ones, leading to a progressively increasing ratio between excitation and inhibition towards excitation, potentially explaining the increased propensity to seizures in chronic undercut cortex.

Systemic Vesicular Stomatitis Virus Selectively Destroys Multifocal Glioma and Metastatic Carcinoma in Brain

Metastatic tumors and malignant gliomas make up the majority of cancers in the brain. They are invariably fatal and there is currently no cure. From in vitro comparisons of a number of viruses, we selected one that appeared the best in selectively killing glioblastoma cells. This replication-competent virus, the glioma-adapted vesicular stomatis virus strain VSVrp30a, was used for in vivo tests with the underlying view that infection of tumor cells will lead to an increase in the number of viruses subsequently released to kill additional tumor cells. Intravenous injection of VSVrp30a expressing a green fluorescent protein reporter, rapidly targeted and destroyed multiple types of human and mouse tumors implanted in the mouse brain, including glioblastoma and mammary tumors. When tumors were implanted both in the brain and peripherally, emulating systemic cancer metastasis, tumors inside and outside the brain were simultaneously infected. Intranasal inoculation, leading to olfactory nerve transport of the virus into the brain, selectively infected and killed olfactory bulb tumors. Neither control cortical wounds nor transplanted normal mouse or human cells were targeted, indicating viral tumor selectivity. Control viruses, including pseudorabies, adeno-associated, or replication-deficient VSV, did not infect the brain tumor. Confocal laser time-lapse imaging through a cranial window showed that intravenous VSV infects the tumor at multiple sites and kills migrating tumor cells. Disrupted tumor vasculature, suggested by dye leakage, may be the port of entry for intravenously delivered VSV. Quantitative PCR analysis of how VSVrp30a selectively infected tumor cells suggested multiple mechanisms, including cell surface binding and internalization.

Tissue reactions to particles of bone-substitute materials in intraosseous and heterotopic sites in rats: discrimination of osteoinduction, osteocompatibility, and inflammation

Two rat models were used to characterize tissue-specific reactions to particles of bone-substitute materials: one for osteocompatibility in a healing tibial wound and the other in a heterotopic, subcutaneous site. Small, unicortical tibial wounds in rats healed spontaneously, beginning with the rapid proliferation of intramedullary woven bone. That temporary bone was resorbed by osteoclasts and finally, the cortical wound was healed with lamellar bone and the medullary space was repopulated with marrow. When various particulate materials were implanted into fresh wounds, three types of reactions were observed. (1) Demineralized bone powder (DBP) and non-resorbable calcium phosphate (nrCP) were incorporated into the reactive medullary and cortical bone. (2) Polymethylmethacrylate (PMMA) particles were surrounded with a fibrous layer, but did not impair bone healing. (3) Polyethylene (PE) shards and resorbable calcium phosphates (rCPs) were inflammatory and inhibited osseous repair. Subcutaneous sites showed osteoinductive, fibrotic, or inflammatory responses to these materials. Only DBP induced endochondral osteogenesis subcutaneously. The nrCP evoked a fibrous reaction. In contrast, rCPs, PMMA, and PE shards generated inflammatory reactions with each particle being surrounded by fibrous tissue and large multinucleated giant cells. In conclusion, only DBP showed osteoinductive as well as osteocompatible properties. The nrCP was osteocompatible. The rCPs stimulated various degrees of inflammatory responses. PMMA was osteocompatible and did not interfere with the bone healing process. PE was not osteocompatible and generated foreign body reactions in both sites. Use of the two sites distinguishes osteoinductive, osteocompatible, and inflammatory properties of particles of bone-substitute materials.

Effect of RGD coating on osteocompatibility of PLGA-polymer disks in a rat tibial wound.

Osteocompatibility of porous polylactic-glycolic acid (PLGA) disks coated with synthetic peptides was assessed in 5-mm diameter unicortical tibial osseous wounds in rats. The coatings consisted of various ratios of peptides including the tripeptide arginine-glycine-aspartic acid (RGD) and the inactive arginine-glycine-glutamic acid (RGE). When left empty, the tibial wounds healed spontaneously with proliferation of intramedullary woven bone within 1 week. The reactive bone was resorbed, and by 3 weeks, the cortical wound was healed with lamellar bone, and the medullary space was repopulated with marrow. When PLGA disks were implanted there was a delay in repair with reduced bone fill and no bone bridging at 3 weeks. When disks were coated with increasing amounts of RGD peptide, there was a biphasic effect on osteocompatibility and on osseous ingrowth. Evaluation at 10 days showed a dose-dependent increase, with 1.5-fold greater osteocompatibility (p < 0.05) and 1.6-fold more osseous ingrowth into the polymer (p < 0.01) than uncoated disks. With more RGD and with undiluted RGE, osteocompatibility and osseous ingrowth were the same as with uncoated disks. At 3 weeks, there were no significant differences among all the groups. These data indicate that RGD coating enhanced early stages of osteocompatibility and ingrowth.

Effects of Age on Gene Expression during Estrogen-Induced Synaptic Sprouting in the Female Rat

Age and estrogen treatment influenced fiber outgrowth and compensatory neuronal sprouting after unilateral entorhinal cortex lesions (ECL) which model Alzheimer disease-like deafferentation in the dentate gyrus of the hippocampus. In young F344 rats (3 months old), ovariectomy (OVX) decreased reactive fiber outgrowth by 60%. Sprouting in middle-aged rats (18 months old) was reduced in intact females; no further reduction was caused by OVX. Several astrocyte mRNAs were measured in the dentate gyrus of young and middle-aged female rats in three different estrogen states (sham OVX, OVX, or OVX + estradiol) 1 week after ECL. Glial fibrillary acidic protein (GFAP) mRNA was twofold greater in middle-aged rats than young, although both ages showed threefold increases in response to ECL. In prior studies GFAP was found to be decreased by estradiol treatment 3–4 days after ECL; in this study GFAP mRNA had returned to sham OVX levels in young rats by 7 days post-ECL. Surprisingly, estradiol treatment increased GFAP mRNA levels by 25% above OVX in middle-aged rats. Apolipoprotein E (apoE) mRNA was decreased 20% by age in the dentate, although both age groups showed a 25% increase in apoE mRNA in response to ECL. Apolipoprotein J (apoJ) mRNA was increased 20% in the dentate gyrus of middle-aged rats, and both age groups responded to ECL with a 65% increase in apoJ mRNA. The estrogen state did not alter levels of either apolipoprotein mRNA in the deafferented dentate. The data suggest that the estrogen-induced decrease of GFAP in response to lesions does not persist at 7 days post-ECL during sprouting. Overall effects of age on the dentate gyrus include elevated GFAP mRNA and decreased apoE mRNA. The cortical wound site showed consistent enhancement of GFAP mRNA in both age groups by estradiol above sham OVX and greater responses in middle-aged rats.

Hemostatic and structural effects of the lyophilized cellulose sponge

Hemostatic effects of oxidized cellulose (Surgicel) are well known. Based on a possible similar effect of a sponge obtained after lyophilization of biosynthetic cellulose, two different experimental studies were planned. Phase I-Pieces of cellulose sponge were inserted into small provoked cortical wounds of twelve dogs. The time elapsed to obtain bloodstill after cortical damage and application of cellulose was observed in every dog, searching to detect any possible hemostatic effect of the material. The animals were sacrificed after 7, 30 and 90 days. An average time of 1 minute was elapsed until bleeding control was achieved. No clinical adverse effect was noticed. Microscopy showed histiocytic and mild foreign body reaction at 7 days, which diminished at 30 days. Almost no reaction surrounded the implant at 90 days. Lyophilized cellulose has a peculiar eosinophilic appearance, composed by thin irregular filaments which diminished their thickness with the time. At 90 days only sparse irregular cellulose filaments could be detected. Phase II-Small equal sponge fragments were inserted in the liver of twelve rats and observed 7, 30 and 90 days. At autopsy, small peritoneal adhesions were noticed at 30 and 90 days. Microscopy showed intense histioplasmocytic and foreign body reaction in all animals mainly at 7 days. In two animals, refringent intracellular cellulose particles were evident inside giant foreign body cells after 90 days. This fact evidences that cellulose can be reabsorbed by phagocytic phenomena when implanted in mammalians. A comparative group with other hemostatic material and the same method must be done to clarify the issue of hemostatic effects of this membrane.

A Cytoplasmic Factor Required for Contraction of the Cleavage Furrow inafMutant Eggs of Xenopus laevis

The abnormal furrow (af) gene was identified through a maternal effect mutation that causes a defect in cell division in Xenopus embryos. In eggs obtained from mutant females (af eggs), polar body formation and cytokinesis are completely inhibited while nuclear division continues uninterrupted. Cleavage furrows are recognized as unpigmented narrow bands on the egg surface but they do not contract. Transfer of cytoplasm from wild-type eggs into af eggs partially rescues contraction of the cleavage furrow. The factor responsible for contraction promoting activity was present in wild-type eggs throughout the first cell division cycle and induced contraction in a dose dependent manner. The factor was characterized as a high molecu- lar weight protein complex that was associated with particulate fraction in the extract. The recovery of con- traction was associated with accumulation of filamentous actin and WGA-binding sites within the cleavage furrow of the af eggs which were normally not enriched for these components. Formation and contraction of a filamentous actin ring during cortical wound healing in af eggs was indistinguishable from that of wild-type eggs. From these results, the af gene product may be specifically required for reorganization of the actin filaments and WGA-binding sites in the cleavage furrow and contraction through these structures during cytokinesis.

The combination of platelet‐derived growth factor‐BB and insulin‐like growth factor‐I stimulates bone repair in adult Yucatan miniature pigs

The combination of insulin-like growth factor-I and platelet-derived growth factor-BB has previously been shown to stimulate healing of soft tissue wounds and the formation of bone and ligament around teeth. The purpose of the present study was to evaluate the effects of platelet-derived growth factor-BB and insulin-like growth factor-I individually and in combination on the healing of osseous wounds. Four standardized cortical wounds were created in each tibia of 11 adult Yucatan miniature pigs. The wounds in one tibia per animal were treated with either purified recombinant human insulin-like growth factor-I, platelet-derived growth factor-BB, or both in a methylcellulose gel. The wounds in each contralateral tibia received placebo gel alone. Coded serial sections of each wound were evaluated by computer-aided histomorphometry 21 days after surgery. The area and perimeter of the newly formed mineralized callus, the thickness of the total callus, and the percentage of mineralized tissue within the callus were significantly increased compared with the values of matched controls only in wounds treated with a combination of insulin-like growth factor-I and platelet-derived growth factor-BB. No significant differences in the measured parameters of callus formation were found in wounds treated with either insulin-like growth factor-I or platelet-derived growth factor-BB alone. Cartilage was present only in sites treated with insulin-like growth factor-I alone. These results suggest that the combination of platelet-derived growth factor-BB and insulin-like growth factor-I stimulates bone formation in wounds in long bones of adult animals and that these growth factors act via different pathways during the repair process.

Transforming growth factor β1 and fibronectin messenger RNA in rat brain: Responses to injury and cell-type localization

Transforming growth factor-β1 rapidly increases in adult rat brain in response to experimental lesions. This study characterized the schedule of changes, regional distribution, and cellular localization of striatal transforming growth factor-β1 messenger RNA and fibronectin messenger RNA following partial striatal deafferentation by frontal cortex ablation. Frontal cortex ablation induced striatal transforming growth factor-β1 messenger RNA elevations that coincided temporally and overlapped anatomically with the course of degeneration of cortico-striatal afferent fibers. Within three days post-lesioning, transforming growth factor-β1 messenger RNA was localized at the cortical wound. By 10 days, the anatomical site of transforming growth factor-β1 messenger RNA expression shifted to the dorsal half of the deafferented striatum and co-localized with OX-42 + immunostained microgliamacrophage at the site of degenerating afferent terminals. Similarly, fibronectin messenger RNA also shifted from the cortical wound to the deafferented striatum by 10 days post-lesioning. Fibronectin messenger RNA was localized to glial fibrillary acidic protein + immunostained astrocytes surrounding degenerating corticostriatal afferents. Infusion of transforming growth factor-β1 peptide elevated striatal and cortical fibronectin messenger RNA. These findings suggest that microglia-macrophage associated with degenerating afferent fibres can upregulate transforming growth factor-β1 messenger RNA and may influence fibronectin messenger RNA synthesis in reactive astrocytes. This study suggests that transforming growth factor-β1 has a role in controlling extracellular matrix synthesis following brain injury, which is analogous to that in peripheral wound healing.

Astrocytic messenger RNA responses to striatal deafferentation in male rat

This investigation describes the schedule and regional distribution of astrocytic responses in striatum following deafferentation by unilateral frontal cortex ablation. In the ipsilateral deafferented striatum, glial fibrillary acidic protein and clusterin (sulfated glycoprotein-2) messengerRNA showed peak elevations by 10 days postlesioning (Northern blots). Vimentin messengerRNA responded faster, with a transient elevation by three days postlesioning. The messengerRNA for glial fibrillary acidic protein, clusterin and vimentin returned toward control levels by 27 days postlesioning. However, the neuronal marker growth-associated protein messengerRNA, was decreased at all postlesion times. By in situ hybridization, the increased glial fibrillary acidic protein messengerRNA and clusterin messengerRNA signals were localized mainly to the dorsal half of the ipsilateral deafferented striatum and followed the same schedule as found by Northern blots. Glial fibrillary acidic protein messengerRNA was widely diffused in the dorsal striatum and was excluded from fascicles of the internal capsule; a similar distribution was found for glial fibrillary acidic protein-immunopositive astrocytes. While clusterin messengerRNA signal showed a distinct clustering, its immunoreactivity appeared as deposits in the deafferented striatal neuropil; Western blots confirmed the immunocytochemical results. By in situ hybridization, vimentin messengerRNA was mostly localized to the cortical wound cavity dorsal to the deafferented striatum and overlapped the distribution of vimentin-immunopositive cells. These findings suggest a coordination of striatal astrocytic messengerRNA responses with the degeneration of corticostriatal afferents. We also compared these same parameters with those from published reports on the hippocampus after deafferenting lesions. Certain astrocyte molecular responses to deafferentation are detected about five days earlier in the hippocampus than in the striatum. This different schedule in response to decortication may pertain to differences in synaptic remodeling in the hippocampus vs striatum.

Receptacle regeneration in Sargassum muticum (Phaeophyta)

Receptacle regeneration in the adventive marine brown alga Sargassum muticum (Yendo) Fensholt (Fucales, Phaeophyta) is examined using light and electron microscopical (SEM, TEM) techniques and laboratory culture studies. After transverse bisection, receptacle regeneration occurred under a wide range of temperatures and at different daylengths but was inhibited under winter conditions (10°C, 8:16 h). Regeneration is a particularly rapid process with mature, zygote-bearing receptacles formed at the cut surface within 21 d at 20°C, 16: 8 h and 88 μmol photons m−2 s−1. Cytological and morphogenetic changes observed after wounding include: the breaking of intercellular plasmodesmatal connections; retraction of cytoplasm and deposition of new fibrillar material beneath the exposed degenerating cell walls, preventing cytoplasmic loss; the formation of a protective wound epidermis over the entire cortical wound surface by finite mitoses in the outermost cell layer; concurrent mitoses to a depth of at least four cells beneath the medullary wound which continue to form a protruding meristematic mound; the development of apical initial cells within the regenerative mound, several of which give rise to new receptacles. Observations on receptacles cut at different points along their length reveal that basal wounds regenerate more slowly than apical wounds, the intact receptacle apex exerting a dominance effect that inhibits regeneration.

Injury-induced neuronotrophic activity in adult rat brain: correlation with survival of delayed implants in the wound cavity

Mechanical or chemical injury to adult rat brain elicited the accumulation in the affected area of trophic activity for cultured parasympathetic, sympathetic, and sensory neurons. Neuronotrophic activity was relatively low both in noninjured brain tissue extracts and in extracts prepared from the tissue surrounding an injury immediately after the lesion was made. However, trophic titers increased considerably over time, first in the brain tissue that formed the walls of the wound and then in the Gelfoam filling the wound cavity. In the tissue adjacent to the injury, trophic titers began to rise immediately after the lesion, reached a maximum 10 days later, and decayed thereafter. In the wound cavity, occupied by Gelfoam, neuronotrophic activity began to increase 6 days postlesion, reached a maximum at day 16 after injury, and decreased at later times. The levels of induced trophic activity appeared to be proportional to the size of the wound. Injury to various brain areas including temporal, entorhinal, occipital, parietal, and frontal cortices, hippocampus, corpus striatum, and cerebellum, all induced a similar increase in neuronotrophic factor(s). Damage to the myelinated fibers of the corpus callosum did not. High trophic titers decayed rapidly with distance from the wound except in areas heavily deafferented by the lesion, where activity also reached high levels. Extracts from all of the above-mentioned brain areas contained toxic activity for cultured spinal cord neurons. The level of neuronotoxic activity was similar both before the lesion and 15 days postlesion, with the possible exception of the corpus callosum. Intraventricular injections of kainic acid at doses which destroy areas CA4, CA3, and part of CA1 of the hippocampus also induced a time-dependent rise of neuronotrophic activity in this structure, comparable to that achieved by mechanical damage. Both kainic acid treatment and mechanical injury cause extensive glial proliferation in the injured and/or deafferented area. The apparent concurrence of glial reaction and increase in neuronotrophic activity suggests that glial cells may be a major source of the induced trophic activity. As an in vivo correlate of cell culture data, the survival of striatal transplants into host cortical wounds was examined. Fragments of embryonic corpus striatum did not survive when transplanted into a freshly made cavity in the entorhinal/occipital cortex of adult rats. Survival was enhanced by introducing a delay between the time at which the wound cavity was made and that at which the striatal tissue was implanted in it.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuronotrophic activity in brain wounds of the developing rat. Correlation with implant survival in the wound cavity

Neuronotrophic activity accumulates in a wound cavity created in the entorhinal/occipital cortex of developing rats. These trophic factors support the survival of neurons in monolayer cultures of chick embryo spinal cord, ciliary ganglion, sympathetic ganglion and dorsal root ganglion, as well as of mouse dorsal root ganglion. Trophic activity was very low both in non-injured brain tissue and in the wound cavity 1 day post-lesion, but it increased 15- to 300-fold during the subsequent 2–5 days. Together with the trophic activity in the wound fluid were other substances which interfered with the survival of spinal cord neurons. The neuronotrophic factors appeared to be proteins immunologically distinct from mouse submaxillary nerve growth factor. Fragments of rat embryo corpus striatum placed in the cortical wound cavity immediately after its formation showed very poor subsequent survival and no innervation of the host hippocampus. However, if implantation was delayed by 3 or 6 days with respect to the time at which the receiving cavity was made, the survival was greatly improved and innervation of the host took place. The time course for the accumulation of the trophic factors in the cavity paralleled the delay leading to increased survival of brain grafts. It is suggested that the neuronotrophic activity accumulating in the wound cavity during the delay period may be responsible for the increased survival of the implants.

An ultrastructural study of the effects of wheat germ agglutinin (WGA) on cell cortex organization during the first cleavage of Xenopus laevis eggs. II. Cortical wound healing.

Uncleaved fertilized eggs of Xenopus laevis treated with wheat germ agglutinin (WGA) have been pricked at the animal pole both inside and outside the regressed furrow region. The wounded cortex of both regions has been studied with the electron microscope and compared with the same region of wounded, untreated eggs. In all 3 cases, filaments are organized in an annular zone in the damaged cortex. When the surface is pricked outside the regressed furrow of WGA-treated embryos, bundles of microfilaments radiate from the ring and extend in deep folds which form a 'star' around the wound at the surface of the embryo. However, when the surface is pricked in the new membrane of the regressed furrow, filaments are intermingled with internalized portions of the plasma membrane. It is suggested that, when the surface is pricked outside the furrow region, more filaments are mobilized to counteract the tangential retraction of the membrane which has acquired more rigidity after WGA binding.

Transmembrane effects of lectins: I. Effects of wheat germ agglutinin and soybean agglutinin on furrow formation and cortical wound healing in Xenopus laevis eggs

Studies on the binding of FITC-WGA and FITC-SBA to normal and cytochalasin (CB)-treated Xenopus eggs have demonstrated the presence of lectin receptors all over the egg surface; there are aggregates of receptors in the region where microvilli are numerous and microfilaments well organized. Addition of WGA or SBA to the incubation medium provokes inhibition of furrow formation provided that the lectins are added before the streak stage, or arrest of contraction when added during furrow formation. This arrest of contraction is followed by furrow regression. The lectins also affect wound healing. All these effects may be explained by an inhibition of membrane proteins movement and an alteration of the relations between the surface and the cytoskeleton.